Polymorphism in the α3 domain of HLA-A molecules affects binding to CD8

Russell D. Salter, Anne M. Norment, Benjamin P. Chen, Carol Clayberger, Alan M. Krensky, Dan R. Littman, Peter Parham*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

219 Scopus citations

Abstract

CYTOTOXIC T lymphocytes (CTL) expressing the CD8 glycoprotein recognize peptide antigens presented by class I major histocompatibility complex (MHC) molecules1,2. This correlation and the absence of CD8 polymorphism led to the hypothesis that CD8 binds to a conserved site of class I MHC molecules. Using a cell-cell binding assay we previously demonstrated specific interaction between human class I MHC (HLA-A,B,C) molecules and CD8 (ref. 3). Subsequent analysis of the products of 17 HLA-A,B alleles revealed a natural polymorphism for CD8 binding in the human population. Two molecules, HLA-Aw68.1 and HLA-Aw68.2, which do not bind CD8, have a valine residue at position 245 whereas all other HLA-A,B,C molecules have alanine. Site-directed mutagenesis shows that this single substitution in the α3 domain is responsible for the CD8 binding phenotype and also affects recognition by alloreactive and influenza-specific CTL. Our results indicate that CD8 binds to the α3 domain of class I MHC molecules.

Original languageEnglish (US)
Pages (from-to)345-347
Number of pages3
JournalNature
Volume338
Issue number6213
DOIs
StatePublished - Jan 1 1989

ASJC Scopus subject areas

  • General

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