THE INTER-LOCUS RECOMBINANT HLA-B-ASTERISK-4601 HAS HIGH SELECTIVITY IN PEPTIDE BINDING AND FUNCTIONS CHARACTERISTIC OF HLA-C

The vast majority of new human HLA class I alleles are formed by conve rsions between existing alleles of the same locus. A notable exception to this rule is HLA-B4601 formed by replacement of residues 66-76 of the alpha 1 helix of B1501 by the homologous segment of Cw*0102. Thi s inter-locus recombination, which brings together characteristic elem ents of HLA-B and HLA-C structure, is shown here to influence function dramatically. Naturally processed peptides bound by B4601 are distin ct from those of its parental allotypes B1501 and Cw*0102 and dominat ed by three high abundance peptides. Such increased peptide selectivit y by B4601 is unique among HLA-A,B,C allotypes. For other aspects of function, presence of the small segment of HLA-C-derived sequence in a n otherwise HLA-B framework converts B4601 to an HLA-C-like molecule. Alloreactive cytotoxic T lymphocytes (CTL), natural killer (NK) cells , and cellular glycosidases all recognize B4601 as though it were an HLA-C allotype. These unusual properties are those of an allotype whic h has frequencies as high as 20% in south east Asian populations and i s associated which predisposition to autoimmune diseases and nasophary ngeal carcinoma.