title: Interactions of HLA-B*4801 with peptide and CD8.
abstract: Functional properties of the B*4801 allotype were investigated using HLA class I-deficient 221 cells transfected with B*4801 cDNA. From pool sequence analysis of endogenously bound peptides, B*4801 was shown to select for nonamer peptides having glutamine or lysine at position 2 and leucine at the carboxyl-terminus. In an in vitro cell-cell binding assay, B*4801 binds CD8 alpha homodimers weakly due to the presence of a threonine residue at position 245 in the alpha 3 domain. A mutant B*4801 molecule in which alanine replaces threonine 245, binds CD8 alpha homodimers at levels comparable to those of other HLA class I allotypes. Despite the low affinity of B*4801 for CD8 alpha, alloreactive T-cells that recognize B*4801 molecules expressed by the 221 transfectant are inhibited by anti-CD8 monoclonal antibodies. Analysis of 25 B*48-expressing individuals from various populations showed threonine 245 was encoded by every B*48 allele.
authors.affiliation: Department of Structural Biology and Microbiology & Immunology, Stanford University School of Medicine, California, USA.
authors.forename: E
authors.initials: E
authors.lastname: Martinez-Naves
authors.forename: L D
authors.initials: LD
authors.lastname: Barber
authors.forename: J A
authors.initials: JA
authors.lastname: Madrigal
authors.forename: C M
authors.initials: CM
authors.lastname: Vullo
authors.forename: C
authors.initials: C
authors.lastname: Clayberger
authors.forename: S C
authors.initials: SC
authors.lastname: Lyu
authors.forename: R C
authors.initials: RC
authors.lastname: Williams
authors.forename: C
authors.initials: C
authors.lastname: Gorodezky
authors.forename: T
authors.initials: T
authors.lastname: Markow
authors.forename: M L
authors.initials: ML
authors.lastname: Petzl-Erler
authors.forename: P
authors.initials: P
authors.lastname: Parham
mesh_terms: D000483:Alleles; D016827:CD8 Antigens / Q000378:metabolism*; D002460:Cell Line; D015235:HLA-B Antigens / Q000378:metabolism*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
chemical_list: D016827:CD8 Antigens; D015235:HLA-B Antigens