Interactions of HLA-B4801 with peptide and CD8

• Published in: Tissue antigens Vol. 50; no. 3; pp. 258 - 264
• Main Authors: Martinez-Naves, E., Barber, L.D., Madrigal, J.A., Vullo, C.M., Clayberger, C., Lyu, S.-C., Williams, R.C., Gorodezky, C., Markow, T., Petzl-Erler, M.L., Parham, P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-1997
• Subjects: Alleles; Amerindian; B4801; CD8; CD8 Antigens - metabolism; Cell Line; HLA class I; HLA-B Antigens - metabolism; Humans; Mutagenesis, Site-Directed; peptide-binding; Polymerase Chain Reaction; Polymorphism, Genetic; Protein Binding; T-Lymphocytes, Cytotoxic - immunology; Transfection
• ISSN: 0001-2815; 1399-0039
• DOI: 10.1111/j.1399-0039.1997.tb02869.x

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 CD8α homodimers weakly due to the presence of a threonine residue at position 245 in the α3 domain. A mutant B*4801 molecule in which alanine replaces threonine 245, binds CD8α homodimers at levels comparable to those of other HLA class I allotypes. Despite the low affinity of B*4801 for CD8α, 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.