Cutting edge: A single MHC anchor residue alters the conformation of a peptide-MHC complex inducing T cells that survive negative selection

Daniel A. Peterson, Richard J. DiPaolo, Osami Kanagawa, Emil R. Unanue

Research output: Contribution to journalArticlepeer-review

Abstract

We generated transgenic mice that expressed hen egg-white lysozyme (HEL) under a class II MHC promoter. The A7 line expressed HEL with a point mutation in the Asp52 residue, the main anchor amino acid responsible for the selection of the chemically dominant family of peptides (52-60) by I-Ak molecules. Mice expressing HEL with Ala52 were completely unresponsive when immunized with the same protein, i.e., HEL A52. However, the same mice immunized with wild-type HEL elicited T cells that recognized a conformation of the 52-61 core sequence uniquely different between Asp52 and Ala52 containing peptides. Importantly, some T cells also recognized the HEL A52 peptide given exogenously but not the same peptide processed from HEL A52 protein. Thus, a core MHC anchor residue influences markedly the specificity of the T cells. We discuss the relevance of these findings to autoimmunity and vaccination with altered peptides.

Original languageEnglish (US)
Pages (from-to)5874-5877
Number of pages4
JournalJournal of Immunology
Volume166
Issue number10
DOIs
StatePublished - May 15 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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