Recognition of altered self major histocompatibility complex molecules modulated by specific peptide interactions

Eur J Immunol. 1996 Apr;26(4):949-52. doi: 10.1002/eji.1830260435.

Abstract

Antigen-specific and major histocompatibility complex (MHC)-restricted recognition by the T cell receptor involves multiple structural contacts over a large molecular surface area. Using a human T cell clone specific for a rubella viral peptide restricted by subsets of HLA DR4 molecules, we identified structurally diverse combinations of peptide-MHC complexes which were functionally equivalent to T cell recognition. Presentation of the rubella-derived peptide on DR4 molecules with an E-74 polymorphism triggered T cell recognition, as did presentation of a single amino acid-substituted peptide in the context of DR4 molecule which lacked the E-74 site. Peptide binding and molecular modeling analysis indicates the structural and functional complementarity of T cell recognition for a specific amino acid side chain, whether contributed by the peptide or by the MHC molecule.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Antigen Presentation*
  • Antigens, Viral / immunology*
  • Autoantigens / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • HLA-DR Antigens / genetics
  • HLA-DR4 Antigen / chemistry
  • HLA-DR4 Antigen / genetics
  • HLA-DR4 Antigen / immunology*
  • HLA-DR4 Antigen / metabolism
  • HLA-DRB1 Chains
  • Humans
  • Lymphocyte Activation
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism
  • Protein Binding
  • Protein Conformation
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Rubella / immunology*
  • Structure-Activity Relationship
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / immunology*

Substances

  • Antigens, Viral
  • Autoantigens
  • HLA-DR Antigens
  • HLA-DR4 Antigen
  • HLA-DRB1 Chains
  • Peptide Fragments
  • Receptors, Antigen, T-Cell, alpha-beta
  • Viral Envelope Proteins
  • E1 envelope protein, Rubella virus