CONSERVED AND VARIABLE RESIDUES WITHIN THE BW4 MOTIF OF HLA-B MAKE SEPARABLE CONTRIBUTIONS TO RECOGNITION BY THE NKB1 KILLER CELL-INHIBITORY RECEPTOR

Allotypes from four divergent HLA-B families (B8, B15, B16, and B27) w ere compared for their inhibition of cytolysis by NK cells expressing the NKB1 receptor. Allotypes differing solely at the Bw4/Bw6 region we re examined as were a more divergent subset of B15 allotypes. The capa city to interact with NKB1 correlated precisely with possession of a B w4 sequence motif at residues 77-83, whereas no correlation was made w ith the peptide-binding specificities of two Bw4 and four Bw6 allotype s of the B15 family. HLA-B allotypes having four different Bw4 motifs were examined and all interact with NKB1. In contrast, HLA-A allotypes , which have a Bw4 motif identical with one of those present in HLA-B, do not. Mutation at leucine 82 and arginine 83, the residues common t o Bw4 motifs, shows they contribute to NKB1 interaction but are not es sential. Three types of polymorphism are implicated in formation of th e ligand recognized by NKB1:ones shared by Bw4 motifs; ones distinguis hing Bw4 motifs; and ones outside the Bw4/Bw6 region that distinguish HLA-B from HLA-A.