Critical role of HLA-DR?* binding peptides' peripheral flanking residues in fully-protective malaria vaccine development

A vaccine candidate component must fit perfectly into the antigen presenting HLA-DR?* molecule's groove (or canonical nonapeptide) peptide binding region (PBR) during antigen presentation to the T-cell receptor (TCR), conforming a specific and stable macromolecular complex and induce an appropriate immune response. Antigen's peripheral flanking residues (PFR, positions (p) -p2 and p10) must thus establish strong interactions with the HLA-DR?* - TCR complex. These amino acids (aa) have specific physico-chemical characteristics enabling differentiation between non-protective but antibody-inducer (NPAI), short-lived protection inducer (SLPI) and long-lasting protection inducer (LLPI) peptides when used as an antimalarial vaccine component. Their identification (through 1H-NMR and Aotus monkey immunization) and proper modification contributes to a logical and rational methodology for long-lasting and protective immunological memory. © 2017 Elsevier Inc.

• Fecha de publicación: 2017
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/23517
• Acceso en línea: https://doi.org/10.1016/j.bbrc.2017.05.123; https://repository.urosario.edu.co/handle/10336/23517
• Palabra clave: HLA DR antigen; Malaria vaccine; HLA DRB1 antigen; Malaria vaccine; Peptide; Animal experiment; Aotus; Article; Binding affinity; Hydrogen bond; Immunogenicity; Immunological memory; Nonhuman; Physical chemistry; Priority journal; Protein structure; Sequence analysis; Structure analysis; Animal; Aotidae; Binding site; Chemistry; Immunology; Synthesis; Animals; Aotidae; Binding Sites; HLA-DRB1 Chains; Malaria Vaccines; Peptides; Amino acid side-chain polarity; Immune protection-inducing peptide structure (IMPIPS); MHCII-peptide-TCR complex; Peripheral flanking residues
• License: Abierto (Texto Completo)