Structural highlights
Function[HA1B_MOUSE] Involved in the presentation of foreign antigens to the immune system. [B2MG_MOUSE] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Publication Abstract from PubMedMHC class I molecules present a variable but limited repertoire of antigenic peptides for T-cell recognition. Understanding how peptide selection is achieved requires mechanistic insights into the interactions between the MHC I and candidate peptides. We find that, at first encounter, MHC I H-2K(b) considers a wide range of peptides, including those with expanded N termini and unfitting anchor residues. Discrimination occurs in the second step, when noncanonical peptides dissociate with faster exchange rates. This second step exhibits remarkable temperature sensitivity, as illustrated by numerous noncanonical peptides presented by H-2K(b) in cells cultured at 26 degrees C relative to 37 degrees C. Crystallographic analyses of H-2K(b)-peptide complexes suggest that a conformational adaptation of H-2K(b) drives the decisive step in peptide selection. We propose that MHC class I molecules consider initially a large peptide pool, subsequently refined by a temperature-sensitive induced-fit mechanism to retain the canonical peptide repertoire. The first step of peptide selection in antigen presentation by MHC class I molecules.,Garstka MA, Fish A, Celie PH, Joosten RP, Janssen GM, Berlin I, Hoppes R, Stadnik M, Janssen L, Ovaa H, van Veelen PA, Perrakis A, Neefjes J Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1505-10. doi:, 10.1073/pnas.1416543112. Epub 2015 Jan 20. PMID:25605945[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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