A SINGLE AMINO-ACID IN THE P58 KILLER-CELL INHIBITORY RECEPTOR CONTROLS THE ABILITY OF NATURAL-KILLER-CELLS TO DISCRIMINATE BETWEEN THE 2 GROUPS OF HLA-C ALLOTYPES

To examine the structural basis for the specific recognition of the MH C class I allotypes HLA-Cw0401 and HLA-Cw*0304 by the killer cell inh ibitory receptors (KIR) cl42 and cl43, respectively, mutant KIR-Ig fus ion proteins were tested by direct binding to cells transfected with s ingle HLA-C alleles. The putative loop region at position 44-46 of KIR contained amino acids that were necessary for the discrimination betw een HLA-Cw0401 and HLA-Cw*0304. Surprisingly, exchanging the methioni ne at position 44 in cl42 with the lysine at position 44 in cl43 was s ufficient to switch the specificity of cl42 from HLA-Cw0401 to HLA-Cw 0304, and vice versa. Thus, a single amino acid in the first Ig domai n of these KIR determines their ability to discriminate between the tw o groups of HLA-C allotypes.