title: Polymorphism in the alpha 3 domain of HLA-A molecules affects binding to CD8.
abstract: Cytotoxic T lymphocytes (CTL) expressing the CD8 glycoprotein recognize peptide antigens presented by class I major histocompatibility complex (MHC) molecules. 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. 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 alpha 3 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 alpha 3 domain of class I MHC molecules.
authors: Department of Cell Biology, Stanford University, California 94305.
authors: R D
authors: RD
authors: Salter
authors: A M
authors: AM
authors: Norment
authors: B P
authors: BP
authors: Chen
authors: C
authors: C
authors: Clayberger
authors: A M
authors: AM
authors: Krensky
authors: D R
authors: DR
authors: Littman
authors: P
authors: P
authors: Parham
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D005805:Genes, MHC Class I; D015234:HLA-A Antigens / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D015234:HLA-A Antigens