spacer HLA-DR1 complexed with a 16 residue HIV capsid peptide bound in a hairpin conformation
Primary citation
Title A hairpin turn in a class II MHC-bound peptide orients residues outside the binding groove for T cell recognition.
Authors Zavala-Ruiz,; Strug,; Walker,; Norris,; Stern,
Journal PROC.NATL.ACAD.SCI.USAsearch vol:101, pag:13279-13284 (2004), Identifiers: PubMed ID (15331779)search DOI (10.1073/pnas.0403371101)
Abstract T cells generally recognize peptide antigens bound to MHC proteins through contacts with residues found within or immediately flanking the seven- to nine-residue sequence accommodated in the MHC peptide-binding groove. However, some T cells require peptide residues outside this region for activation, the structural basis for which is unknown. Here, we have investigated a HIV Gag-specific T cell clone that requires an unusually long peptide antigen for activation. The crystal structure of a minimally antigenic 16-mer bound to HLA-DR1 shows that the peptide C-terminal region bends sharply into a hairpin turn as it exits the binding site, orienting peptide residues outside the MHC-binding region in position to interact with a T cell receptor. Peptide truncation and substitution studies show that both the hairpin turn and the extreme C-terminal residues are required for T cell activation. These results demonstrate a previously unrecognized mode of MHC-peptide-T cell receptor interaction.
MeSH terms Amino Acid Sequencesearch, Antigen Presentationsearch, Binding Sitessearch, Crystallizationsearch, HIV Core Protein p24search, HLA-DR1 Antigensearch, Humanssearch, Lymphocyte Activationsearch, Molecular Sequence Datasearch, Peptide Fragmentssearch, Protein Conformationsearch, T-Lymphocytessearch
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