Conformational Isomers of a Peptide-Class II Major Histocompatibility Complex

Immunol Rev. 2005 Oct;207:293-313. doi: 10.1111/j.0105-2896.2005.00298.x.

Abstract

The relative plasticity of peptide binding to class II major histocompatibility complex (MHC) molecules permits formation of multiple conformational isomers by the same peptide and MHC molecule; such conformers are specifically recognized by distinct subsets of T cells. Here, we review current knowledge and recent advances in our understanding of peptide-class II MHC conformational isomerism and the mechanisms that generate distinct MHC-peptide conformers. We focus on our studies of two T-cell subsets, type A and B, which recognize distinct conformers of the dominant epitope of hen egg white lysozyme presented by I-A(k). These conformers form via different pathways and in distinct intracellular vesicles: the type A conformer forms in late endosomes upon processing of native protein, while the more flexible type B conformer forms in early endosomes and at the cell surface. In this process, H2-DM acts as a conformational editor, eliminating the type B conformer in late endosomes. Type B T cells constitute a significant component of the naïve T-cell repertoire; furthermore, self-reactive type B T cells escape negative selection and are present in abundance in the periphery. Ongoing studies should elucidate the role of type B T cells in immunity to pathogens and in autoimmune pathology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Histocompatibility Antigens Class II / immunology*
  • Humans
  • Isomerism
  • Lymphocyte Activation / immunology
  • Models, Immunological*
  • Muramidase / immunology
  • Muramidase / metabolism
  • Peptides / immunology*
  • Protein Binding / immunology
  • Protein Conformation
  • T-Lymphocyte Subsets / immunology*

Substances

  • Histocompatibility Antigens Class II
  • Peptides
  • hen egg lysozyme
  • Muramidase