3D Analysis of the TCR/pMHCII Complex Formation in Monkeys Vaccinated with the First Peptide Inducing Sterilizing Immunity against Human Malaria

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 beta 1*0403 molecules with high capacity. Spectratyping analysis showed a preferential usage of V beta 12 and V beta 6 TCR gene families in 67% of HLA-DR beta 1*0403-like genotyped monkeys. Docking of peptide 24112 into the HLA-DR beta 1*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.

• Fecha de publicación: 2010
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/8806
• Acceso en línea: https://doi.org/10.1371/journal.pone.0009771; http://repository.urosario.edu.co/handle/10336/8806
• Palabra clave: Receptor de células T; Mhc Clase-ii; Monos del nuevo mundo; Las células rojas de la sangre; Plasmodium falciparum; Estructura cristalina; Hla-dr4 Dra-asterisco-0101; Aotus-nancymaae; Aminoácidos; Diversidad; Enfermedades; Malaria; Plasmodio; Enfermedades autoinmunes; Inmunología; T-cell-receptor; Mhc Class-ii; New-world Monkeys; Red-blood-cells; Plasmodium-falciparum; Crystal-structure; Hla-dr4 Dra-asterisk-0101; Aotus-nancymaae; Amino-acids; Diversity
• License: Abierto (Texto completo)