3d analysis of the tcrpmhcii complex formation in monkeys vaccinated with the first peptide inducing sterilizing immunity against human malariatcrpmhcii复杂的3 d分析形成猴子与第一肽诱导接种疫苗对人类疟疾消毒免疫力.pdf

3D Analysis of the TCR/pMHCII Complex Formation in Monkeys Vaccinated with the First Peptide Inducing Sterilizing Immunity against Human Malaria 1,2. ´ 1,2. ´ 1,2 1 Manuel A. Patarroyo , Adriana Bermudez , Carolina Lopez , Gloria Yepes , Manuel E. Patarroyo1,3* ´ ´ ´ ´ 1 Fundacion Instituto de Inmunologıa de Colombia, Bogota, Cundinamarca, Colombia, 2 Universidad del Rosario, Bogota, Cundinamarca, Colombia, 3 Universidad ´ Nacional de Colombia, Bogota, Cundinamarca, Colombia Abstract 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-DR b1*0403 molecules with high capacity. Spectratyping analysis showed a preferential usage of Vb12 and Vb6 TCR gene families in 67% of HLA- DRb1*0403-like genotyped monkeys. Docking of peptide 24112 into the HLA-DRb1*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 method