A binding site for the T-cell co-receptor CD8 on the alpha 3 domain of HLA-A2

Nature. 1990 May 3;345(6270):41-6. doi: 10.1038/345041a0.


Adhesion measurements between CD8 and 48 point mutants of HLA-A2.1 show that the CD8 alpha-chain binds to the alpha 3 domain of HLA-A2.1. Three clusters of alpha 3 residues contribute to the binding, with an exposed, negatively charged loop (residues 223-229) playing a dominant role. CD8 binding correlates with cytotoxic T-cell recognition and sensitivity to inhibition by anti-CD8 antibodies. Impaired alloreactive T-cell recognition of an HLA-A2.1 mutant with reduced affinity for CD8 is not restored by functional CD8 binding sites on an antigenically irrelevant class I molecule. Therefore, complexes of CD8 and the T-cell receptor bound to the same class I major histocompatibility complex molecule seem to be necessary for T-cell activation.

Publication types

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

MeSH terms

  • Antigens, CD / immunology*
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • CD8 Antigens
  • Cell Line
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology*
  • Humans
  • Lymphocyte Activation
  • Molecular Structure
  • Mutation
  • Protein Conformation
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Transfection


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD8 Antigens
  • HLA-A2 Antigen
  • Receptors, Antigen, T-Cell