Class I MHC expression by target cells inhibits lysis mediated by natural killer (NK) cells. In previous studies we demonstrated that a subset of HLA-B*2705-specific NK clones recognized only 1 of 4 peptides bound to HLA-B*2705 expressed by TAP-deficient cell lines (RMA-S). To extend this observation we screened a panel of B*2705-specific NK clones with 14 synthetic peptides corresponding to the sequence of endogenous peptides eluted from B*2705 and with 23 peptides carrying a single amino acid substitution in the sequence of the best protective peptide (FRYNGLIHR). Only residues at position 7 and 8 affected recognition by NK clones. Interestingly, side chain P8 interacts with residues 76, 77 and 80 of the MHC-class I molecules, a stretch of sequence known to influence recognition of HLA-B and HLA-C alleles by NK cells. Thus, the peptide sequence is an important component of B*2705 structures that can be recognized by NK inhibitory receptors. To test whether discrimination among peptides bound to B*2705 could be achieved by a single p70 receptor expressed in a given NK clone, the functional reconstitution system with vaccinia virus encoded KIR was used. NK clones that did not recognize HLA-B*2705 were chosen for expression of a single KIR (encoded by cDNA ell 1) that is specific for HLA-B*2705. Vac-11 infected NK clones recognized B*2705 molecules expressed on wild-type cells, but not on TAP-deficient cells. Furthermore, Vac-11 infected NK clones recognized B*2705 molecules on TAP-deficient cells loaded with the protective peptide FRYNGLIHR, but not those loaded with non-protective peptides. Thus, a single p70 KIR can discriminate among peptides bound to HLA-B*2705.
|Publication status||Published - 1996|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology