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bioRxiv · 10.1101/550889

HLA-C-restricted presentation of a conserved bacterial epitope to an innate NK cell receptor

Sim, M. J. W.·Rajagopalan, S.·Altmann, D. M.·Boyton, R. J.·Sun, P. D.·Long, E. O.
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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. 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.

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Sim, M. J. W., Rajagopalan, S., Altmann, D. M., Boyton, R. J., Sun, P. D., Long, E. O.. 2019-02-15. HLA-C-restricted presentation of a conserved bacterial epitope to an innate NK cell receptor. https://doi.org/10.1101/550889

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