The inter-locus recombinant HLA-B super()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 conversions between existing alleles of the same locus. A notable exception to this rule is HLA-B super(*)4601 formed by replacement of residues 66-76 of the alpha 1 helix of B super(*)1501 by the homologous segment of Cw super(*)0102. This inter-locus recombination, which brings together characteristic elements of HLA-B and HLA-C structure, is shown here to influence function dramatically. Naturally processed peptides bound by B super(*)4601 are distinct from those of its parental allotypes B super(*)1501 and Cw super(*)0102 and dominated by three high abundance peptides. Such increased peptide selectivity by B super(*)4601 is unique among HLA-A,B,C allotypes. For other aspects of function, presence of the small segment of HLA-C-derived sequence in an otherwise HLA-B framework converts B super(*)4601 to an HLA-C-like molecule. Alloreactive cytotoxic T lymphocytes (CTL), natural killer (NK) cells, and cellular glycosidases all recognize B super(*)4601 as though it were an HLA-C allotype. These unusual properties are those of an allotype which has frequencies as high as 20% in south east Asian populations and is associated with predisposition to autoimmune diseases and nasopharyngeal carcinoma.