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Natural killer (NK) cell clones have been previously described which are inhibited by HLA-C alleles with Asn77-Lys80 (NK1-specific cells) or by HLA-C alleles with Ser77-Asn80 (NK2-specific cells). In the present work, the generation of NK cells with HLA-B-related specificities was attempted by stimulation of a Bw4 homozygous responder by a Bw6 homozygous donor. Two NK clones were found, which were inhibited by HLA-Bw4 (but not by HLA-Bw6) allotypes and by some HLA-A allotypes that share the Bw4 public epitope. Inhibition of NK cell-mediated lysis strongly correlated with the presence of an Ile residue at position 80 of the protective allele. These NK cell clones define a new specificity termed NK3.

NK3-specific natural killer cells are selectively inhibited by Bw4-positive HLA alleles with isoleucine 80.