A binding site for the T-cell co-receptor CD8 on the α3 domain of HLA-A2

Russell D. Salter*, Richard J. Benjamin, Pamela K. Wesley, Sarah E. Buxton, Thomas P J Garrett, Carol Clayberger, Alan M. Krensky, Anne M. Norment, Dan R. Littman, Peter Parham

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

466 Scopus citations

Abstract

Adhesion measurements between CD8 and 48 point mutants of HLA-A2.1 show that the CD8 α-chain binds to the α3 domain of HLA-A2.1. Three clusters of α3 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.

Original languageEnglish (US)
Pages (from-to)41-46
Number of pages6
JournalNature
Volume345
Issue number6270
DOIs
StatePublished - Jan 1 1990

ASJC Scopus subject areas

  • General

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