Polymorphisms in pockets of major histocompatibility complex class I molecules influence peptide preference

Eric M. Rohren, Larry R. Pease, Hidde L. Ploegh, Ton N.M. Schumacher

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

The set of peptides that is bound by a given major histocompatibility complex class I product can be described by one or two properly spaced anchor residues, and two properly spaced peptide termini, approximately 8-10 residues apart. Using radiolabeled peptide libraries, we examined whether mutations in those “pockets” in class I Kb molecules that do not seem critically involved in the interaction with the peptide anchor residues, do exert an effect on the set of preferred peptides. We find that mutations in all the pockets found in the structure of Kb have a significant effect on the peptide preference of the molecule, and their recognition by cytotoxic T cells. Alterations in substrate specificity are also observed for mutations involving residues that interact with main chain atoms in both peptide termini. These findings challenge a static view of the interaction of peptide termini with their respective pockets in the class I molecule, and imply a role for the minor pockets in peptide selectivity.

Original languageEnglish (US)
Pages (from-to)1713-1721
Number of pages9
JournalJournal of Experimental Medicine
Volume177
Issue number6
DOIs
StatePublished - Jun 1 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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