CHARACTERIZATION OF THE PEPTIDE-BINDING SPECIFICITY OF HLA-B-ASTERISK-7301

Previous studies showed the human MHC class I heavy chain HLA-B7301 h as a sequence very divergent from other class I alleles. Despite the u nusual sequence, we predicted B7301 would retain the peptide-binding function typical of other HLA-A, B and C glycoproteins, and sequence s imilarity to B2705 in a region of the peptide-binding site known as t he B pocket suggested B7301 would bind peptides with Arg at position 2. To test this hypothesis, the peptide-binding specificity of B7301 was investigated. Sequence analysis of peptides bound endogenously by B7301 indeed found selectivity for nonamer peptides possessing Arg at position 2 and a preference for small nonpolar residues such as Pro o r Ala at the C terminus was also revealed. B7301 therefore possesses the potential to function as a conventional antigen presenting class I glycoprotein. Functional similarities between B7301 and B*2705 are d iscussed in the context of the association of B27 subtypes with susce ptibility to ankylosing sponylitis and arthritic diseases.