TY - JOUR
T1 - 3D Analysis of the TCR/pMHCII Complex Formation in Monkeys Vaccinated with the First Peptide Inducing Sterilizing Immunity against Human Malaria
AU - Patarroyo, Manuel A.
AU - Bermúdez, Adriana
AU - López, Carolina
AU - Yepes, Gloria
AU - Patarroyo, Manuel E.
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2010
Y1 - 2010
N2 - T-cell receptor gene rearrangements were studied in Aotus monkeys developing high antibody titers and sterilizing immunity against the Plasmodium falciparum malaria parasite upon vaccination with the modified synthetic peptide 24112, which was identified in the Merozoite Surface Protein 2 (MSP-2) and is known to bind to HLA-DRβ1*0403 molecules with high capacity. Spectratyping analysis showed a preferential usage of Vβ12 and Vβ6 TCR gene families in 67% of HLADRβ1* 0403-like genotyped monkeys. Docking of peptide 24112 into the HLA-DRβ1*0401-HA peptide-HA1.7TCR complex containing the VDJ rearrangements identified in fully protected monkeys showed a different structural signature compared to nonprotected monkeys. These striking results show the exquisite specificity of the TCR/pMHCII complex formation needed for inducing sterilizing immunity and provide important hints for a logical and rational methodology to develop multiepitopic, minimal subunit-based synthetic vaccines against infectious diseases, among them malaria.
AB - T-cell receptor gene rearrangements were studied in Aotus monkeys developing high antibody titers and sterilizing immunity against the Plasmodium falciparum malaria parasite upon vaccination with the modified synthetic peptide 24112, which was identified in the Merozoite Surface Protein 2 (MSP-2) and is known to bind to HLA-DRβ1*0403 molecules with high capacity. Spectratyping analysis showed a preferential usage of Vβ12 and Vβ6 TCR gene families in 67% of HLADRβ1* 0403-like genotyped monkeys. Docking of peptide 24112 into the HLA-DRβ1*0401-HA peptide-HA1.7TCR complex containing the VDJ rearrangements identified in fully protected monkeys showed a different structural signature compared to nonprotected monkeys. These striking results show the exquisite specificity of the TCR/pMHCII complex formation needed for inducing sterilizing immunity and provide important hints for a logical and rational methodology to develop multiepitopic, minimal subunit-based synthetic vaccines against infectious diseases, among them malaria.
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U2 - 10.1371/journal.pone.0009771
DO - 10.1371/journal.pone.0009771
M3 - Article
C2 - 20333301
AN - SCOPUS:79952117436
SN - 1932-6203
VL - 5
JO - PLOS ONE
JF - PLOS ONE
IS - 3
M1 - e9771
ER -
