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It has been reported that autoantibodies against the β2-adrenergic receptors are involved in the pathology of allergic disorders and of Chagas' disease. Therefore, the immune response against a peptide (H26Q) corresponding to the putative second extracellular loop of the human β2-adrenergic receptor, which could be a target for autoantibody attack, was analysed in view of its possible immunogenicity. The free peptide induced a T cell-mediated humoral response in the context of three different murine MHC haplotypes. The T cell epitope was found to be localized in the N-terminal region of the peptide. Highly specific T helper cells were capable of stimulating B cells with the potential to generate a large antibody repertoire reactive with the loop peptide. MoAbs were screened to analyse this B cell response for antibodies potentially interfering with receptor function and a MoAb was found that impaired ligand binding to the receptor. [ABSTRACT FROM AUTHOR]

The effect of Trypanosoma cruzi infection on the ability of mature and immature murine peritoneal macrophage (MPM) subpopulations to catabolize the bacteriophage lambda repressor cI protein (cI) has been investigated. The capacity of infected MPM to present the cI and to stimulate various CD4+, I-Ad- or I-Ed-restricted T-cell hybridomas specific for cI was also assessed. Our results show that the radioiodinated cI uptake and catabolism decreased sharply after infection of MPM with T. cruzi. A cI presentation deficiency appeared in mature and immature MPM infected with T. cruzi trypomastigotes. The ability of infected MPM to bind immunogenic cI (12-26) peptides to the plasma membrane Ia molecules was also altered, especially in immature MPM, as shown with paraformaldehyde prefixed MPM, suggesting that these MPM only have a few functional Ia molecules on their membrane. The reduced capacity of cI presentation to the I-Ed-restricted B26. I hybridomas by infected MPM subpopulations was comparable to that of the I-Ad-restricted B24.4 and 826.2 T cells. The percentage of major histocompatibility complex (MHC) class II-positive MPM was also reduced after T. cruzi infection. The percentage of positive interleukin-2 receptor (IL-2R) MPM was sharply lowered in infected cells, even with a pre- or a post-interferon-γ (IFN-γ) activation. Finally, inhibition of prostaglandin with' indomethacin, or of nitric oxide with N-monomethyl-L-arginine, or of tumour necrosis factor-α (TNF-α) with specific monoclonal antibodies did not restore the cI presentation capacities of the MPM subpopulations. Taken together, these results suggest that T. cruzi infection induces a reduced capacity for macrophages to take up and catabolize antigen, resulting in a deficient antigen processing and presentation of the derived immunogenic peptides to specific CD4+ T-helper type-1 cell hybridomas. The decreased cI presenting capacity was a function of the cell's burden and maturity. [ABSTRACT FROM AUTHOR]

Cell-mediated immunity directed against human papillomavirus 16 (HPV-16) antigens was studied in 16 patients affected with classic vulvar intra-epithelial neoplasia (VIN), also known as bowenoid papulosis (BP). Ten patients had blood lymphocyte proliferative T cell responses directed against E6/2 (14–34) and/or E6/4 (45–68) peptides, which were identified in the present study as immunodominant among HPV-16 E6 and E7 large peptides. Ex vivo enzyme-linked immunospot–interferon (IFN)-γ assay was positive in three patients who had proliferative responses. Twelve months later, proliferative T cell responses remained detectable in only six women and the immunodominant antigens remained the E6/2 (14–34) and E6/4 (45–68) peptides. The latter large fragments of peptides contained many epitopes able to bind to at least seven human leucocyte antigen (HLA) class I molecules and were strong binders to seven HLA-DR class II molecules. In order to build a therapeutic anti-HPV-16 vaccine, E6/2 (14–34) and E6/4 (45–68) fragments thus appear to be good candidates to increase HPV-specific effector T lymphocyte responses and clear classic VIN (BP) disease lesions. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome induce account for over 40 million deaths in the past 20 years. Given that the currently available treatments to prevent HIV transmission and disease are not effective in eradicating the virus, vaccination likely represents the only efficacious adapted response to the global impact of this infection. This paper reviews the challenges encountered in the development of an HIV vaccine as well as the different vaccine approaches and main HIV vaccine candidates evaluated in clinical trials. Current knowledge and key points: In spite the tremendous progress in HIV research, the major challenges that are encountered in the development of an HIV vaccine remain of scientific order and include viral specificities, absence of correlates of immune protection and limitations of existing animal models. Over 30 vaccine candidates have been evaluated in clinical trials. These vaccine approaches include the use of recombinant envelope proteins, DNA vaccines, live-vectored recombinant vaccines, subunit vaccines and prime-boost regimens combining various vaccine candidates. Although the protective efficacy of these candidate vaccines has yet to be demonstrated, some vaccination regiments appear to dampen initial viremia and prolong disease-free survival. Future prospects and projects: Faced with the challenges in developing an HIV vaccine, international consortia and new methodologies have been proposed in order to accelerate the development and screening process of new candidate HIV vaccines. Moreover, in the absence of a protective vaccine, the impact of a vaccine that confers partial protection needs to be seriously considered. [Copyright &y& Elsevier]

Polyclonal antibodies were raised in rabbits by immunization with free peptides corresponding to positions 197-222 of the human β1-adrenergic receptor (β1 peptide) and the corresponding sequence (172-197) of the human β2-adrenergic receptor (β2 peptide). While the β2 peptide yielded antibodies that cross-reacted with the β1 peptide, the antibodies against the β1 peptide did not cross-react with the β2 sequence. Cross-reactivity of the anti-β2 peptide antibodies and the selectivity of the anti-β1 peptide antibodies were also revealed in the recognition by immunoblots of the β1- and β2-adrenergic receptors of different species or of the receptor gene products expressed in a bacterial vector. These antibodies could be used immunohistochemically to visualize the β-adrenergic receptors on rabbit heart. The anti-β2 peptide antibodies did not show any functional effect on the β-adrenergic receptors; the anti-β1 peptide antibodies were able to displace agonist affinity to higher values. Recognition of truncated peptides by the anti-β1 and anti-β2 peptide antibodies suggested that the cross-reaction of the anti-β2 peptide antibodies was due to the recognition of a common epitope on the C-terminal part of the peptides. The anti-β1 peptide antibodies recognized the N-terminal part of the peptide better than the C-terminal part. These results suggest that the second extracellular loop postulated in the structure of the human β-adrenergic receptor contains the T and B cell epitopes necessary for induction of an immune response. The selectivity and the functional properties of the antibodies raised against that loop in the β1 adrenergic receptor could have relevance in induction of auto antibodies in certain cardiomyopathic conditions. [ABSTRACT FROM AUTHOR]