INTERACTIONS OF HLA-B-ASTERISK-4801 WITH PEPTIDE AND CD8

Functional properties of the B4801 allotype were investigated using H LA class I-deficient 221 cells transfected with B4801 cDNA. From pool sequence analysis of endogenously bound peptides, B4801 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, B4801 binds CD8 alpha homodimers weakly due to the presence o f a threonine residue at position 245 in the alpha(3) domain. A mutant B4801 molecule in which alanine replaces threonine 245, binds CD8 al pha homodimers at levels comparable to those of other HLA class I allo types. Despite the low affinity of B4801 for CD8 alpha, alloreactive T-cells that recognize B4801 molecules expressed by the 221 transfect ant are inhibited by anti-CD8 monoclonal antibodies. Analysis of 25 B 48-expressing individuals from various populations showed threonine 24 5 was encoded by every B48 allele.