25 results on '"Kanduc D"'
Search Results
2. Proteome-Wide Epstein-BarrVirus Analysis of Peptide Sharing with Human Systemic Lupus Erythematosus Autoantigens.
- Author
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Kanduc D
- Subjects
- Complement C4 immunology, Cross Reactions immunology, Databases, Factual, Herpesvirus 4, Human immunology, Humans, Interleukin-10 immunology, Autoantigens immunology, Epstein-Barr Virus Infections immunology, Lupus Erythematosus, Systemic immunology, Peptides immunology, Proteome
- Abstract
Background: Although cross-reactions between Epstein-Barr virus (EBV) and human systemic lupus erythematosus (SLE) autoantigens occur, a complete analysis of the potential EBV peptide cross-reactome has not been performed., Objectives: To analyze the whole EBV proteome searching for peptides common to SLE-related proteins and endowed with an immunological potential., Methods: Fifty-one SLE-related proteins were analyzed for hexapeptide sharing with EBV proteome using publicly available databases., Results: An extremely high number of hexapeptides are shared between 34 human SLE autoantigens and EBV proteins. The peptide sharing mostly occurs with complement components C4 and Interleukin-10 (IL-10)., Conclusions: This study thoroughly describes the EBV vs. SLE autoantigens peptide overlap and powerfully supports cross-reactivity as a major mechanism in EBV-associated SLE etiopathogenesis.
- Published
- 2019
3. Describing the potential crossreactome between mumps virus and spermatogenesis-associated proteins.
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Kanduc D
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- Antigens, Viral chemistry, Cross Reactions, Humans, Infertility, Male immunology, Infertility, Male virology, Male, Peptide Fragments chemistry, Peptide Fragments immunology, Proteome immunology, Seminal Plasma Proteins chemistry, Sequence Alignment, Sequence Analysis, Protein, Viral Proteins chemistry, Viral Proteins immunology, Antigens, Viral immunology, Mumps virus immunology, Proteome analysis, Seminal Plasma Proteins immunology, Spermatogenesis immunology
- Abstract
This study documents that mumps virus shares several peptide sequences with human proteins that, when altered, may be involved in oligospermia/azoospermia, sterility and testicular atrophy. Examples are sperm flagellar protein 2 and spermatogenesis and centriole-associated protein 1. The data invite to further investigate crossreactivity as a potential mechanism linking anti-mumps immune responses, alterations of spermatogenesis-associated antigens and male fertility disorders.
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- 2014
- Full Text
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4. Evidence for a vast peptide overlap between West Nile virus and human proteomes.
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Capone G, Pagoni M, Delfino AP, and Kanduc D
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- Amino Acid Sequence, Databases, Protein, Humans, Sequence Analysis, Protein, West Nile virus physiology, Oligopeptides chemistry, Proteome chemistry, Viral Proteins chemistry, West Nile virus chemistry
- Abstract
The primary amino acid sequence of West Nile virus (WNV) polyprotein, GenBank accession number M12294, was analyzed by computional biology. WNV is a mosquito-borne neurotropic flavivirus that has emerged globally as a significant cause of viral encephalitis in humans. Using pentapeptides as scanning units and the perfect peptide match program from PIR International Protein Sequence Database, we compared the WNV polyprotein and the human proteome. WNV polyprotein showed significant sequence similarities to a number of human proteins. Several of these proteins are involved in embryogenesis, neurite outgrowth, cortical neuron branching, formation of mature synapses, semaphorin interactions, and voltage dependent L-type calcium channel subunits. The biocomputional study suggest that common amino acid segments might represent a potential platform for further studies on the neurological pathophysiology of WNV infections., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
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- 2013
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5. Peptide sharing between Bordetella pertussis proteome and human sudden death proteins: a hypothesis for a causal link.
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Capone G and Kanduc D
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- Antibodies, Bacterial immunology, Autoantibodies immunology, Bacterial Proteins immunology, Bordetella pertussis immunology, Cross Reactions, Humans, Peptides immunology, Bacterial Proteins analysis, Bordetella pertussis chemistry, Death, Sudden etiology, Peptides analysis, Proteome analysis, Sequence Homology, Amino Acid
- Abstract
Aim: To explore the molecular basis of the relationship between Bordetella pertussis infection and sudden death., Methods: B. pertussis proteins were analyzed for amino acid sequence identity to a set of 67 human proteins that, when altered, have been associated with sudden death., Results: More than 82,000 pentapeptides are shared between B. pertussis proteins and sudden death-associated antigens., Conclusion: Results suggest that a possible link between B. pertussis infection and sudden death might be represented by potential immunological cross-reactions occurring between B. pertussis proteins and human proteins associated to sudden death.
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- 2013
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6. A quantitative description of the peptide sharing between poliovirus and Homo sapiens.
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Novello G, Capone G, Fasano C, Bavaro SL, Polito AN, and Kanduc D
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- Humans, Peptides immunology, Poliovirus immunology, Viral Proteins immunology, Genome, Viral, Peptides genetics, Poliovirus genetics, Proteome genetics, Viral Proteins genetics
- Abstract
In the present study, we analyze the peptide commonality between poliovirus polyprotein and the human proteins. We report on the following findings: (1) the extent of polio peptide overlap on the human proteome is high, and involves the entire viral polyprotein; (2) viral peptide matching affects human proteins linked to fundamental cellular functions. The data may help to further our understanding of the relationships between poliovirus and the human host.
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- 2012
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7. Charting the peptide crossreactome between HIV-1 and the human proteome.
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Lucchese G, Stufano A, Calabro M, and Kanduc D
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- Cross Reactions, Humans, HIV-1 metabolism, Peptides metabolism, Proteome
- Abstract
This paper defines potential peptide cross-reactivity between HIV-1 and the human host. Specifically, the amino acid primary sequence of HIV-1, isolate CDC-451, was analyzed for potential immunopathological relationships with the human proteome. The results revealed that: 1) HIV-1 shares 50 heptapeptides and three octapeptides with the human proteome; 2) 34 of the 50 shared heptapeptides are experimentally validated epitopes targeted by immune responses following HIV-1 infection; 3) the viral heptapeptide epitopes are present in human proteins that, when altered, are associated with disease characteristics of acquired immunodeficiency syndrome (AIDS) such as CD4+ cell loss, encephalopathy, schizophrenia, myopathy, cardiovascular disorders, hypertension, corneal diseases, diarrhea, lymphoma, and bladder cancer; 4) at the pentapeptide level, the viral-versus-human overlap is extensive (14,227 matches), with the viral pentapeptides disseminated throughout 10,312 human proteins. The findings are discussed in relationship to HIV-1 escape from immune surveillance, adjuvant-induced HIV-1 immunogenicity, autoimmune cross-reactions following human hyperimmune responses against HIV-1, and AIDS.
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- 2011
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8. Pentapeptide commonality between Corynebacterium diphtheriae toxin and the Homo sapiens proteome.
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Bavaro SL and Kanduc D
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- Amino Acid Sequence, Cross Reactions, Diphtheria Toxin immunology, Humans, Immunotherapy methods, Molecular Sequence Data, Peptides immunology, Proteins immunology, Diphtheria Toxin chemistry, Peptides analysis, Proteins chemistry, Proteome
- Abstract
Cross-reactivity may affect diagnostic tests and cause harmful autoimmune reactions following immunotherapy. To predict potential cross-reactivity and search for safe immunotherapeutic approaches, we analyzed sequence identity between microbial antigens and the human proteome. Using diphtheria toxin (DT) as a model, we examined its patterns of identity with human proteins at the pentapeptide level. DT shares 503 pentapeptides with the human proteome, while only 31 pentapeptides are unique to the toxin. DT pentapeptide identity involves multiple/repeated matches in human proteins (a total of 4966 occurrences). Human proteins containing bacterial peptide matches include antigens linked to fundamental cellular functions, such as cell cycle control, proliferation, development and differentiation. The data presented in this article offer a rational basis for designing peptide-based vaccines that specifically target DT and thus eliminate the potential risk of cross-reactivity with human proteins. More generally, this study proposes a methodological approach for avoiding cross-reactivity in immune reactions.
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- 2011
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9. Potential cross-reactivity between HPV16 L1 protein and sudden death-associated antigens.
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Kanduc D
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- Antigens immunology, Capsid Proteins immunology, Capsid Proteins metabolism, Cardiovascular Diseases physiopathology, Connectin, Cross Reactions immunology, Humans, Muscle Proteins chemistry, Muscle Proteins metabolism, Oncogene Proteins, Viral immunology, Oncogene Proteins, Viral metabolism, Papillomavirus Vaccines immunology, Protein Kinases chemistry, Protein Kinases metabolism, Sequence Analysis, Protein, Antigens chemistry, Capsid Proteins chemistry, Death, Sudden, Cardiac pathology, Oncogene Proteins, Viral chemistry, Proteome chemistry
- Abstract
In exploring the primary sequence of the human papilloma virus (HPV) 16 major capsid L1 protein for peptide sharing with human proteins, we find that 34 pentamers from the viral capsid protein are shared with human proteins that, when altered, have been linked to short QT syndrome, arrhythmogenic cardiac disorders, cardiovascular diseases and sudden death. In particular, nine out of the 34 viral pentamers are present in a human protein, titin, alterations of which have been linked to cardiac failure and sudden cardiac death. The present data may help evaluate the potential crossreactivity risks in anti-tumor vaccination protocols based on HPV16 L1 protein.
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- 2011
10. Codon number shapes peptide redundancy in the universal proteome composition.
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Kusalik A, Trost B, Bickis M, Fasano C, Capone G, and Kanduc D
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- Amino Acid Sequence, Computational Biology, Databases, Protein, Humans, Molecular Sequence Data, Sequence Analysis, Protein, Codon, Peptides genetics, Proteome analysis, Proteome genetics
- Abstract
The proteomes catalogued in the UniRef100 database were collected into a single proteome set and examined for actual versus theoretical pentapeptide occurrences. We found a highly diversified degree of pentapeptide redundancy. Numerically, 953 pentamers are expressed only once in the protein world, whereas 103 pentamers occur more than 50,000 times. Moreover, it seems that 417 potentially possible pentapeptides are not present in the protein world. On the whole, tracing the redundancy profile of the protein world as a function of pentapeptide occurrences reveals a quasi-Gaussian curve, with tails representing scarcely and repeatedly occurring 5-mers. Analysis of physico-chemical-biological parameters shows that codon number is the main factor influencing and favoring specific pentapeptide frequencies in the universal proteome composition. That is, when compared to the set of never-expressed 5-mers, the pentapeptides frequently represented in the universal proteome are endowed with a higher number of multi-codonic amino acids. In contrast, the bulkiness degree and the hydrophobicity level play a smaller role. Unexpectedly, the heat of formation of pentapeptide appears to have the least influence.
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- 2009
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11. Proteome-based epitopic peptide scanning along PSA.
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Stufano A and Kanduc D
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- Amino Acid Sequence, Animals, Genes, MHC Class II, HLA Antigens genetics, HLA Antigens metabolism, Humans, Male, Mice, Molecular Sequence Data, Epitopes analysis, Epitopes genetics, Peptides genetics, Peptides immunology, Prostate-Specific Antigen genetics, Prostate-Specific Antigen immunology, Proteome analysis
- Abstract
The specific definition of the immunogenic peptide repertoire from tumor-associated-antigens (TAAs) is of crucial importance for designing effective immunotherapeutical treatments. Multiple mechanisms, at different levels and in complementary manners, contribute to the generation of immunogenic peptides. Using as an experimental model the prostate specific antigen (PSA) and a murine monoclonal antibody (MAb) raised against human PSA, the role of PSA peptide 1) similarity to the murine proteome, 2) affinity to H2-Ad/Ed molecules, and 3) proteasomal cleavage pattern were investigated. We report that the core of the interaction between the anti-PSA MAb ER-PR8 and the prostatic antigen is located in the pentapeptide motif PSA(27-31)GGWEC. The pentapeptide motif is characterized by having no sequence similarity to the murine proteome and a low number of potential proteolytic sites.
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- 2009
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12. Epitopic peptides with low similarity to the host proteome: towards biological therapies without side effects.
- Author
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Kanduc D
- Subjects
- Apoptosis Regulatory Proteins, Autoimmunity, BRCA2 Protein immunology, Dendritic Cells immunology, Humans, Vaccines immunology, Epitopes, B-Lymphocyte, Peptides immunology, Proteome
- Abstract
Background: A structured analysis of the literature indicates that a low level of sequence similarity to the host proteome modulates the B cell epitope pool in the humoral immune response toward protein antigens. From a clinical point of view, low-similarity peptides might have strong repercussions for the rational development of peptide-based treatments for cancer, autoimmunity and infectious diseases. The most attractive feature of the similarity concept is that it appears to guarantee the highest specificity and lowest cross-reactivity when designing effective, safe and theoretically infallible (immuno)therapeutic tools., Objective/methods: This review describes the research pathway from protein- to peptide-based therapies., Results/conclusions: Using the breast-cancer-associated BRCA2 protein as a model, the principle of sequence uniqueness is defined as the rationale for a pharmacological platform that might yield improved results in both patient survival and quality of life.
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- 2009
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13. P-170 peptides with low similarity to the human proteome: tracing an effective and safe biological way towards effective and safe cancer chemotherapy.
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Kanduc D, Novello G, and Mazzanti R
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- ATP Binding Cassette Transporter, Subfamily B, Amino Acid Sequence, Antineoplastic Agents adverse effects, Databases, Protein, Epitopes genetics, Glycoproteins antagonists & inhibitors, Glycoproteins immunology, Humans, Molecular Sequence Data, Peptide Fragments chemistry, Peptide Fragments immunology, Antibodies, Blocking pharmacology, Antineoplastic Agents therapeutic use, Drug Resistance, Multiple drug effects, Drug Resistance, Neoplasm drug effects, Glycoproteins chemistry, Peptide Fragments pharmacology, Proteome chemistry
- Abstract
We propose low-similarity P-170 peptide-based antibodies to neutralize the multidrug resistance phenomenon and, consequently, improve the treatment regimens for cancer chemotherapy. As a first step in the experimental validation of this approach, we report on the similarity analysis of the P-170 primary amino acid structure versus the human proteome and describe peptide motifs uniquely owned by the human P-170 glycoprotein.
- Published
- 2009
14. Massive peptide sharing between viral and human proteomes.
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Kanduc D, Stufano A, Lucchese G, and Kusalik A
- Subjects
- Amino Acid Sequence, Databases, Protein, Humans, Molecular Sequence Data, Peptides metabolism, Viral Proteins metabolism, Peptides genetics, Proteome, Viral Proteins genetics
- Abstract
Thirty viral proteomes were examined for amino acid sequence similarity to the human proteome, and, in parallel, a control of 30 sets of human proteins was analyzed for internal human overlapping. We find that all of the analyzed 30 viral proteomes, independently of their structural or pathogenic characteristics, present a high number of pentapeptide overlaps to the human proteome. Among the examined viruses, human T-lymphotropic virus 1, Rubella virus, and hepatitis C virus present the highest number of viral overlaps to the human proteome. The widespread and ample distribution of viral amino acid sequences through the human proteome indicates that viral and human proteins are formed of common peptide backbone units and suggests a fluid compositional chimerism in phylogenetic entities canonically classified distantly as viruses and Homo sapiens. Importantly, the massive viral to human peptide overlapping calls into question the possibility of a direct causal association between virus-host sharing of amino acid sequences and incitement to autoimmune reactions through molecular recognition of common motifs.
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- 2008
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15. Mapping the human proteome for non-redundant peptide islands.
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Capone G, De Marinis A, Simone S, Kusalik A, and Kanduc D
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- Amino Acid Motifs genetics, Amino Acid Motifs immunology, Antigens immunology, Humans, Peptides immunology, Proteome immunology, Antigens genetics, Peptides genetics, Proteome genetics, Sequence Analysis, Protein methods
- Abstract
We describe immune-proteome structures using libraries of protein fragments that define a structural immunological alphabet. We propose and validate such an alphabet as i) composed of letters of five consecutive amino acids, pentapeptide units being sufficient minimal antigenic determinants in a protein, and ii) characterized by low-similarity to human proteins, so representing structures unknown to the host and potentially able to evoke an immune response. In this context, we have thoroughly sifted through the entire human proteome searching for non-redundant protein motifs. Here, for the first time, a complete sequence redundancy dissection of the human proteome has been conducted. The non-redundant peptide islands in the human proteome have been quantified and catalogued according to the amino acid length. The library of uniquely occurring n-peptide sequences that was obtained is characterized by a logarithmic decrease of the number of non-redundant peptides as a function of the peptide length. This library represents a highly specific catalogue of molecular protein signatures, the possible use of which in cancer/autoimmunity research is discussed, with a major focus on non-redundant dodecamer sequences.
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- 2008
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16. Widespread and ample peptide overlapping between HCV and Homo sapiens proteomes.
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Kusalik A, Bickis M, Lewis C, Li Y, Lucchese G, Marincola FM, and Kanduc D
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- Amino Acid Motifs, Amino Acid Sequence, Humans, Molecular Sequence Data, Sequence Homology, Amino Acid, Hepacivirus chemistry, Peptides chemistry, Proteome analysis
- Abstract
Alignment of protein sequences is fundamental in analyzing homology, evolutionary events and functional relationships. Searching for the epitopic peptide platform underlying hepatitis C virus (HCV) infection and autoimmune phenomena, we have used sequence-sequence peptide matching to compare the HCV polyprotein sequence to the human proteome. The following results were obtained: (1) pentamers from HCV polyprotein have a widespread and high level of similarity to a large number of human proteins (19,605 human proteins, that is 57.6% of the human proteome); (2) remarkable similarity between the two proteomes persists even using longer peptide motifs as probes for identity scanning; (3) only a limited number of HCV pentameric fragments have no similarity to the human host, so representing molecular sequence signatures of the virus. We conclude that the widespread sharing of numerous perfect exact matches between HCV and human proteomes might explain HCV persistence in humans.
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- 2007
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17. Non-redundant peptidomes from DAPs: towards "the vaccine"?
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Kanduc D, Lucchese A, and Mittelman A
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- Amino Acid Sequence, Animals, Humans, Mice, Molecular Sequence Data, Peptides genetics, Proteome genetics, Vaccines chemistry, Antibody Specificity, Databases, Genetic, Peptides immunology, Proteome immunology, Vaccines immunology
- Abstract
Experimental analyses and literature survey reveal low-redundancy to the host proteins as a common denominator of immunogenic sequences mapped along tumor-, autoimmune-, and infectious disease-associated-proteins. The hypothesis that immunogenicity of peptide sequences is linked to proteomic redundancy is discussed.
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- 2007
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18. Definition of anti-tyrosinase MAb T311 linear determinant by proteome-based similarity analysis
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Jörg Willers, Alberta Lucchese, Darja Kanduc, Abraham Mittelman, Reinhard Dummer, Willers, J, Lucchese, Alberta, Mittelman, A, Dummer, R, and Kanduc, D.
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Proteomics ,medicine.drug_class ,Tyrosinase ,Molecular Sequence Data ,Tyrosinase Peptide ,Dermatology ,Biology ,Monoclonal antibody ,Biochemistry ,Epitope ,Epitopes ,Mice ,Antigen ,Antigens, Neoplasm ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Melanoma ,Molecular Biology ,Peptide sequence ,Monophenol Monooxygenase ,Immunogenicity ,H-2 Antigens ,Antibodies, Monoclonal ,Peptide Fragments ,Proteome ,Immunology ,Epitope Mapping - Abstract
Using non-self discrimination as a driving force in generating peptide immunogenicity, we have developed a computer-assisted proteomic analysis in order to identify the protein antigenic regions that have evoked humoral response. The purpose of this study was to further validate the computational analysis for melanoma-associated antigens and, at the same time, to assess the efficacy of the methodology in defining antigenic regions of autoantigens associated to autoimmune diseases. To achieve this two-fold objective, we have examined the enzyme tyrosinase, a protein that represents an important autoantigen in patients with vitiligo or melanoma. Here, we report that the antigenic linear determinant of the monoclonal antibody (Mab) T311 raised against the melanoma/vitiligo tyrosinase autoantigen is located in the low similarity 15-mer amino acid sequence tyrosinase 233-247 IPYWDWRDAEKCDIC, within the fragment 237-247. These data confirm non-similarity to the host proteome as a factor that participates in shaping peptide immune reactivity and may be a first step towards designing tyrosinase antigenic peptides to be used for (i) direct neutralization of harmful melanocytes-attacking autoantibodies in vitiligo, or (ii) production of antibodies against tyrosinase-positive melanomas. Moreover tyrosinase peptide antigens might be used as key tools in studying the boundaries between self-tolerance and autoimmunity phenomena.
- Published
- 2005
19. Role of MHC II affinity and molecular mimicry in defining anti-HER-2/neu MAb-3 linear peptide epitope
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Darja Kanduc, Abraham Mittelman, Stefan Stevanovic, Animesh A. Sinha, Alberta Lucchese, Lucchese, Alberta, Stevanovic, S, Sinha, Aa, Mittelman, A, and Kanduc, D.
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Receptor, ErbB-2 ,Physiology ,medicine.drug_class ,Blotting, Western ,Molecular Sequence Data ,Peptide ,Biology ,medicine.disease_cause ,Monoclonal antibody ,Binding, Competitive ,Biochemistry ,Epitope ,Epitopes ,Mice ,Cellular and Molecular Neuroscience ,Endocrinology ,Immune system ,Antigen ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Amino Acid Sequence ,chemistry.chemical_classification ,Mice, Inbred BALB C ,Molecular Mimicry ,Histocompatibility Antigens Class II ,Antibodies, Monoclonal ,Computational Biology ,Binding potential ,Molecular biology ,Cell biology ,Molecular mimicry ,chemistry ,Proteome ,Electrophoresis, Polyacrylamide Gel ,Oligopeptides ,Epitope Mapping - Abstract
With the aid of computational biology, we have studied the possibility of predicting the peptides able to evoke humoral immune response by using as experimental model the human HER-2/neu breast cancer-associated antigen. We already demonstrated that HER-2/neu peptides, that are the target of humoral human and mouse immune responses, correspond to those sequences having a low degree of sequence similarity to host's proteome. Here we report that the linear peptide determinant of the anti-HER-2/neu MAb-3 is characterized by a low degree of sequence similarity to mouse proteome in combination with high binding potential to specific MHC II molecule.
- Published
- 2003
20. Individuation of monoclonal anti-HPV16 E7 antibody linear peptide epitope by computational biology
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Darja Kanduc, Abraham Mittelman, Alberta Lucchese, Kanduc, D, Lucchese, Alberta, and Mittelman, A.
- Subjects
Physiology ,Papillomavirus E7 Proteins ,Molecular Sequence Data ,Peptide ,Computational biology ,Immunodominance ,Biology ,medicine.disease_cause ,Biochemistry ,Epitope ,Epitopes ,Mice ,Cellular and Molecular Neuroscience ,Endocrinology ,medicine ,Animals ,Amino Acid Sequence ,Peptide sequence ,chemistry.chemical_classification ,MHC class II ,Antibodies, Monoclonal ,Computational Biology ,Oncogene Proteins, Viral ,MHC restriction ,Molecular mimicry ,chemistry ,Proteome ,biology.protein ,Epitope Mapping - Abstract
We applied computational biology to identify the linear amino acid sequence recognized by a mouse monoclonal antibody raised against the full length HPV16 E7 oncoprotein. Computer-assisted search for the epitopic peptide used two parameters: the capability of E7 peptides to bind to MHC class II molecules, and the similarity level of the oncoprotein sequence to the mouse proteome. We report that anti-E7 mAb recognized the peptide having both high binding potential to MHC II molecules and low level of molecular mimicry to mouse proteome. Peptide ability to bind to MHC II molecules appears a necessary but not sufficient condition to determine peptide immunodominance, by needing to be supported by a low degree of peptide similarity to the host’s proteome.
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- 2001
21. Correlating low-similarity peptide sequences and HIV B-cell epitopes
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Alberta Lucchese, Darja Kanduc, Rosario Serpico, Yehuda Shoenfeld, Kanduc, D, Serpico, Rosario, Lucchese, Alberta, and Shoenfeld, Y.
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Autoimmune cross-reactions ,Proteome ,HIV Antigens ,Immunology ,Human immunodeficiency virus (HIV) ,Peptide ,HIV Infections ,Computational biology ,Anti-HIV vaccines ,Biology ,HIV Antibodies ,medicine.disease_cause ,Pentapeptide repeat ,Epitope ,Immune system ,Similarity (network science) ,Proteomic similarity ,medicine ,Immunology and Allergy ,Animals ,Humans ,Amino Acid Sequence ,chemistry.chemical_classification ,Sequence uniqueness ,Virology ,chemistry ,Antibody Formation ,biology.protein ,HIV-1 ,HIV-1 B-cell epitopes ,Epitopes, B-Lymphocyte ,Antibody - Abstract
Although a large number of human immunodeficiency virus-1 (HIV-1) derived B-cell epitopes has been experimentally identified, the structural requirements underlying HIV humoral immune response remain unknown. Here, we review the current literature on HIV B-cell epitopes as catalogued in the www.hiv.lanl.gov/content/immunology website, searching for common structural and/or functional immunogenic motifs. The analysis of HIV antibody data documents that the linear determinants recognized by human or murine humoral immune responses, are (or harbor) pentapeptide fragments with no or only very low similarity to the respective host proteome. The present literature analysis provides relevant insights that may be applied to design anti-HCV therapeutic approaches exempt from autoimmune collateral effects.
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- 2007
22. Non-redundant peptidomes from DAPs: towards 'the vaccine'?
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Darja Kanduc, Abraham Mittelman, Alberta Lucchese, Kanduc, D, Lucchese, Alberta, and Mittelman, A.
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Vaccines ,Proteome ,Immunogenicity ,Immunology ,Molecular Sequence Data ,Common denominator ,Computational biology ,Biology ,complex mixtures ,Virology ,Mice ,Antibody Specificity ,Databases, Genetic ,Redundancy (engineering) ,Immunology and Allergy ,Animals ,Humans ,Amino Acid Sequence ,Literature survey ,Peptides ,Host protein - Abstract
Experimental analyses and literature survey reveal low-redundancy to the host proteins as a common denominator of immunogenic sequences mapped along tumor-, autoimmune-, and infectious disease-associated-proteins. The hypothesis that immunogenicity of peptide sequences is linked to proteomic redundancy is discussed.
- Published
- 2007
23. Computational peptide dissection of Melan-a/MART-1 oncoprotein antigenicity
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Raj K. Tiwari, Alberta Lucchese, Abraham Mittelman, Darja Kanduc, Jan Geliebter, Tiwari, R, Geliebter, J, Lucchese, Alberta, Mittelman, A, and Kanduc, D.
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Models, Molecular ,Antigenicity ,Proline ,Proteome ,Physiology ,medicine.drug_class ,Immunoblotting ,Peptide ,Biology ,Monoclonal antibody ,Biochemistry ,Epitope ,Major Histocompatibility Complex ,Epitopes ,Mice ,Cellular and Molecular Neuroscience ,MART-1 Antigen ,Endocrinology ,Antigen ,Antigens, Neoplasm ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Melanoma ,Peptide sequence ,Immunoassay ,Oncogene Proteins ,chemistry.chemical_classification ,B-Lymphocytes ,Antibodies, Monoclonal ,Computational Biology ,Molecular biology ,Neoplasm Proteins ,Molecular Weight ,Epitope mapping ,chemistry ,Peptides ,Melanoma-Specific Antigens ,Epitope Mapping ,Protein Binding - Abstract
We have mapped the linear antigenic determinant of a commercial MAb raised in the mouse against the melanoma-associated-antigen Melan-A/MART-1. The B cell epitope on the Melan-A/MART-1 oncoprotein is located in the 15-mer amino acid sequence 101-115 PPAYEKLSAEQSPPP, within residues 102-106. The definition of the antigenic sequence on Melan-A/MART-1 oncoprotein was reached following analyses of MHC II binding potential and similarity level to the mouse proteome, that put into evidence the 15-mer amino acid sequence 101-115 PPAYEKLSAEQSPPP as the top scoring peptide in binding H2-A(d) molecules and the epitopic sequence residues 102-106 (i.e., the peptide sequence PAYEK) as having low-similarity level to the mouse proteome. Dot-blot epitope mapping immunoassay identified proline residue 102 as critical, based on its effect on antibody recognition. The present study adds to previous companion reports in validating the hypothesis that low-similarity to the host's proteome and binding potential to MHC II molecules are essential concurring factors in the modulation of the pool of epitopic sequences.
- Published
- 2004
24. Monoclonal and polyclonal humoral immune response to EC HER-2/NEU peptides with low similarity to the host's proteome
- Author
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Darja Kanduc, Animesh A. Sinha, Alberta Lucchese, Abraham Mittelman, Mittelman, A, Lucchese, Alberta, Sinha, Aa, and Kanduc, D.
- Subjects
Male ,Cancer Research ,Proteome ,medicine.drug_class ,Receptor, ErbB-2 ,Uterine Cervical Neoplasms ,Breast Neoplasms ,Enzyme-Linked Immunosorbent Assay ,Monoclonal antibody ,Epitopes ,Mice ,Antigen ,Human proteome project ,medicine ,Animals ,Humans ,Mice, Inbred BALB C ,biology ,Immunogenicity ,Antibodies, Monoclonal ,Computational Biology ,Prostatic Neoplasms ,Molecular biology ,Epitope mapping ,Oncology ,Polyclonal antibodies ,Immunology ,Antibody Formation ,Colonic Neoplasms ,biology.protein ,Female ,Antibody ,Oligopeptides ,Epitope Mapping - Abstract
We are studying peptide immunogenicity as a function of the similarity level to the host's proteome. By using as a model the breast/prostate cancer-associated HER-2/neu antigen, we analyzed the monoclonal and polyclonal humoral immune responses against HER-2/neu peptide motifs not shared with the host proteome. We show here that (i) a mouse monoclonal antibody (MAb) raised against the extracellular domain (EC) of human HER-2/neu oncoprotein recognized a linear peptide motif endowed with low similarity level to the mouse proteome; (ii) likewise, human sera from breast/prostate cancer patients preferentially recognized peptide fragments from the EC of the HER-2/neu oncoprotein having sequences that are not present in the human proteome. Together with previous results obtained in other disease models (cervical cancer-associated HPV16 E7 oncoprotein and Pemphigus vulgaris auto-antigen desmoglein-3), the present data suggest that a low level of sequence similarity to the host's proteome might be an important factor in shaping the pool of B cell epitopes.
- Published
- 2002
25. Sequence uniqueness as a molecular signature of HIV-1-derived B-cell epitopes
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Alberta Lucchese, Yehuda Shoenfeld, Vito Crincoli, Rosario Serpico, Darja Kanduc, Lucchese, Alberta, Serpico, Rosario, Crincoli, V, Shoenfeld, Y, and Kanduc, D.
- Subjects
Proteomics ,Mutation rate ,Immunology ,Computational biology ,Antibodies ,Epitope ,Mice ,Retrovirus ,Antibody Specificity ,Sequence Analysis, Protein ,Animals ,Humans ,Immunology and Allergy ,Amino Acid Sequence ,Databases, Protein ,Peptide sequence ,AIDS Vaccines ,Pharmacology ,Sequence Homology, Amino Acid ,biology ,Immunogenicity ,biology.organism_classification ,Vaccine therapy ,Vaccination ,Drug Design ,Proteome ,HIV-1 ,Epitopes, B-Lymphocyte ,Sequence Alignment - Abstract
The complex pathophysiology of human immunodeficiency virus (HIV) infection and the relatively high mutation rate of the retrovirus make it challenging to design effective anti-HIV vaccines. Several attempts have been made during the last decades to elucidate the enigmatic immunology of HIV infection and to predict potential immunogenic peptides for active vaccination using bioinformatic analysis methods. The results obtained to date to address this important problem are scarce. In this study, we exploit available HIV databases and analyse previously characterized HIV-encoded linear B-cell epitopes for their amino acid sequence similarity to the human or murine host proteome. We obtained further documentation that the HIV-derived antibody-targeted sequences mostly coincide with peptide areas rarely shared with the host proteins. In toto, our past and present data give clear-cut support to the statement that low-similarity to the host proteome is a major mechanism in defining viral peptide immunogenicity and indicate a possible way for inducing effective, high-titer, and non-cross-reactive antibodies to be used in anti-HIV vaccine therapy.
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