@article {Sim550889, author = {Malcolm J. W. Sim and Sumati Rajagopalan and Daniel M. Altmann and Rosemary J. Boyton and Peter D. Sun and Eric O. Long}, title = {HLA-C-restricted presentation of a conserved bacterial epitope to an innate NK cell receptor}, elocation-id = {550889}, year = {2019}, doi = {10.1101/550889}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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. {\textquoteleft}Self{\textquoteright} 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.}, URL = {https://www.biorxiv.org/content/early/2019/02/15/550889}, eprint = {https://www.biorxiv.org/content/early/2019/02/15/550889.full.pdf}, journal = {bioRxiv} }