1. TCR-contacting residues orientation and HLA-DRβ* binding preference determine long-lasting protective immunity against malaria
- Author
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Manuel A. Patarroyo, Martha Patricia Alba, Yahson Varela, Adriana Bermúdez, Carlos F. Suárez, and Manuel E. Patarroyo
- Subjects
0301 basic medicine ,Antimalarial-vaccine ,Unclassified drug ,HLA-DR beta-Chains ,Plasma protein binding ,Parasitemia ,Biochemistry ,Malaria vaccine ,Immunological memory ,Monkey model ,Protein structure ,Binding protein ,Receptors ,Provocation test ,Priority journal ,Innate immunity ,Antibody titer ,Structure activity relation ,Quinine ,Quinina ,Aotus ,Major histocompatibility antigen class 2 ,Chemistry ,Immunogenic protection inducing peptide structure ,Aotus trivirgatus ,Antibody response ,Hla drb4 antigen ,Multiprotein complex ,Protein Binding ,Recombinant protein ,Stereochemistry ,Parasite antibody ,Binding sites ,Immunology ,Immunologic memory ,Plasmodium falciparum ,Biophysics ,Hla drb3 antigen ,Receptors, Antigen, T-Cell ,Human leukocyte antigen ,Hla-dr beta-chains ,Biology ,Antigen binding ,Article ,Rotamer-orientation ,Binding site ,03 medical and health sciences ,Structure-Activity Relationship ,Immune system ,antigen ,t-cell ,Immunogenetics ,innate ,Structure–activity relationship ,Protein binding ,Animals ,Animal model ,Animal experiment ,Hla dr antigen ,MHC-II ,Molecular Biology ,T-cell-receptor ,Memoria Inmunológica ,Malaria falciparum ,Binding Sites ,030102 biochemistry & molecular biology ,Animal ,T-cell receptor ,Immunity ,Cell Biology ,biology.organism_classification ,Nonhuman ,Structure-activity relationship ,Immunity, Innate ,Malaria ,030104 developmental biology ,Binding affinity ,T lymphocyte receptor ,Hla drb5 antigen ,Controlled study ,Immunologic Memory ,Lymphocyte antigen receptor - Abstract
Fully-protective, long-lasting, immunological (FPLLI) memory against Plasmodium falciparum malaria regarding immune protection-inducing protein structures (IMPIPS) vaccinated into monkeys previously challenged and re-challenged 60 days later with a lethal Aotus monkey-adapted P. falciparum strain was found to be associated with preferential high binding capacity to HLA-DR?1* allelic molecules of the major histocompatibility class II (MHC-II), rather than HLA-DR?3*, ?4*, ?5* alleles. Complete PPIIL 3D structure, a longer distance (26.5 Å ± 1.5 Å) between residues perfectly fitting into HLA-DR?1*PBR pockets 1 and 9, a gauche? rotamer orientation in p8 TCR-contacting polar residue and a larger volume of polar p2 residues was also found. This data, in association with previously-described p3 and p7 apolar residues having gauche+ orientation to form a perfect MHC-II-peptide-TCR complex, determines the stereo-electronic and topochemical characteristics associated with FPLLI immunological memory. © 2016 Elsevier Inc.
- Published
- 2016