A single residue polymorphism at DR beta 37 affects recognition of peptides by T cells

Hum Immunol. 1997 Apr 15;54(1):30-9. doi: 10.1016/s0198-8859(97)00013-x.


Single amino acid polymorphism at residue 37 of the HLA-DR beta chain (DR beta 37) between DRB1*0406 and 0403 markedly influences susceptibility to the insulin autoimmune syndrome. We investigated the effects of DR beta 37 polymorphism regarding recognition of nonself peptides by a T-cell clone, YN5-32, specific to a streptococcal peptide (M12p54-68) presented by the DRB1*0406 molecule. YN5-32 responded better to M12p54-68 presented by allogeneic DRB1*0403 with a single Tyr-substitution at DR beta 37-Ser of the DRB1*0406 molecule. One hundred and fifty-four peptides carrying single residue substitutions at each of the core residues 57-65 of M12p54-68, were tested for full agonistic and TCR antagonistic activities. Forty-six peptides showed full agonism, 34 analogues exhibited TCR antagonism, and 45 analogues exhibited neither full agonism nor TCR antagonism, irrespective of the presenting molecules (DRB1*0406 or 0403). On the other hand, 29 analogue peptides substituted at each of residues 57-63 of M12p54-68 were recognized differently by YN5-32, depending on the presenting molecules. These observations indicate that 1) single amino acid polymorphism (Ser-Tyr) at the DR beta 37 residue induced a conformational change distinguished by TCR in some but not all peptides; and 2) these conformational changes were observed even in analogue peptides carrying single residue substitutions at residues far from a putative DR beta 37 contact site. These findings provide further evidence for altered human T-cell responses induced by TCR ligands with minor modifications.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Amino Acids / genetics*
  • Antigen Presentation / genetics
  • Clone Cells
  • Epitopes / genetics
  • HLA-DR Antigens / genetics*
  • HLA-DR Antigens / immunology*
  • HLA-DRB1 Chains
  • Humans
  • Isoantigens / genetics
  • Molecular Sequence Data
  • Peptides / agonists
  • Peptides / antagonists & inhibitors
  • Peptides / immunology*
  • Polymorphism, Genetic
  • Receptors, Antigen, T-Cell / agonists
  • Receptors, Antigen, T-Cell / antagonists & inhibitors
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*


  • Amino Acids
  • Epitopes
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Isoantigens
  • Peptides
  • Receptors, Antigen, T-Cell