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TCR-contacting residues orientation and HLA-DR?* binding preference determine long-lasting protective immunity against malaria

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Alba, Martha P.
Suarez, Carlos F.
Varela, Yahson
Patarroyo, Manuel A.
Bermudez, Adriana
Patarroyo, Manuel E.



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Elsevier B.V.

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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.
Palabras clave
Binding protein , innate , t-cell , Hla drb4 antigen , Hla drb5 antigen , Immunogenic protection inducing peptide structure , Major histocompatibility antigen class 2 , Malaria vaccine , Multiprotein complex , Parasite antibody , Quinine , Recombinant protein , T lymphocyte receptor , Unclassified drug , Hla dr antigen , Lymphocyte antigen receptor , Protein binding , Animal experiment , Animal model , Antibody response , Antibody titer , Antigen binding , Article , Binding affinity , Controlled study , Immunogenetics , Immunological memory , Malaria falciparum , Monkey model , Nonhuman , Parasitemia , Plasmodium falciparum , Priority journal , Provocation test , Animal , Aotus , Binding site , Chemistry , Immunological memory , Immunology , Innate immunity , Malaria , Structure activity relation , Animals , Aotus trivirgatus , Binding sites , Hla-dr beta-chains , Immunity , Immunologic memory , Malaria , Plasmodium falciparum , Protein binding , Receptors , Structure-activity relationship , Antimalarial-vaccine , Immunological memory , Mhc-ii , Rotamer-orientation , T-cell-receptor
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