PT - JOURNAL ARTICLE AU - Malcolm J. W. Sim AU - Sumati Rajagopalan AU - Daniel M. Altmann AU - Rosemary J. Boyton AU - Peter D. Sun AU - Eric O. Long TI - HLA-C-restricted presentation of a conserved bacterial epitope to an innate NK cell receptor AID - 10.1101/550889 DP - 2019 Jan 01 TA - bioRxiv PG - 550889 4099 - http://biorxiv.org/content/early/2019/02/15/550889.short 4100 - http://biorxiv.org/content/early/2019/02/15/550889.full AB - The killer-cell Ig-like receptor (KIR) family, expressed mainly in natural killer (NK) cells, includes an activation receptor of unknown function, KIR2DS4. Here we show that KIR2DS4 is restricted by HLA-C*05:01 with a strong preference for tryptophan at position 8 of 9-mer peptides. ‘Self’ peptides with Trp8 eluted from HLA-C*05:01 are rare and only one out of 12 bound KIR2DS4. An HLA-C*05:01-peptide complex that bound KIR2DS4 was sufficient for strong activation of primary KIR2DS4+ NK cells, independently of coactivation by other receptors and of prior NK cell licensing. A highly conserved sequence in bacterial recombinase A, which is essential for DNA repair and survival, includes an epitope that bound to HLA-C*05:01 and activated KIR2DS4+ NK cells. Thus, in addition to their established role in defense against viruses and cancer, NK cells may have also evolved to detect and respond to hundreds of bacterial species through recognition of a conserved RecA epitope.