Amino-terminal flanking residues determine the conformation of a peptide-class II MHC complex

Scott B. Lovitch, Zheng Pu, Emil R. Unanue

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

The peptide spanning residues 48-62 of hen egg white lysozyme presented by I-Ak molecules gives rise to two T cell populations, types A and B, that recognize distinct conformers of the complex generated in late and recycling endosoines. The class II-like accessory molecule H2-DM functions as a conformational editor, eliminating the type B conformer in late endosomes. Here, we show that the conformation of the complex, and its susceptibility to editing by HI-DM, are determined by peptide amino-terminal lanking residues. Elimination of these residues abolished editing, permitting formation of the type B conformer in late endosomes. Substitutions at P(-2) affected the stability of the type B conformer, preventing its formation and/or editing, without hindering peptide binding or formation of the type A conformer of the complex. We conclude that interactions involving amino-terminal flanking residues stabilize peptide-MHC conformers and confer resistance to editing by H2-DM, influencing the nature of the T cell repertoire.

Original languageEnglish
Pages (from-to)2958-2968
Number of pages11
JournalJournal of Immunology
Volume176
Issue number5
DOIs
StatePublished - Mar 1 2006

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