Abstract
Natural killer cell tolerance is maintained by the interaction of killer inhibitory receptors (KIRs) with self-major histocompatibility complex class I gene products. A subset of T cells also expresses inhibitory receptors, but the functional significance of these receptors on T cells is unclear1,2,3. Here we show that, in the absence of T-cell receptor (TCR) engagement, KIRs expressed on CD8+ T cells are slowly downregulated by KIR ligands expressed on antigen-presenting cells. The resulting expression levels of KIR are no longer able to inhibit T-cell function. In contrast, TCR engagement sustains KIR expression, and re-induces functional levels of KIR expression after ligand-induced downregulation of KIR. Our data indicate that KIR expression on CD8+ T cells in vivo may be maintained through continuous encounters with antigen. As KIR-mediated inhibition of T-cell activation can be bypassed at high antigen concentrations, dynamic KIR expression may mediate T-cell tolerance to self-antigens by sparing self-reactive T cells, thus enabling them to mediate potentially useful immune functions to quantitatively or qualitatively different antigens.
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Acknowledgements
We thank A. Vitiello for 721.221 transfected with HLA A2.1; E. Noessner for the HLA-Cw*0702 construct; Soo Young Yang for the mAb 4E; and S. Carlsson for the anti-lamp-1 antiserum. We thank E. Long for his critical reading of the manuscript. B. Huard thanks F. Triebel for hosting the final experiments of this project in his laboratory.
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Huard, B., Karlsson, L. KIR expression on self-reactive CD8+ T cells is controlled by T-cell receptor engagement. Nature 403, 325–328 (2000). https://doi.org/10.1038/35002105
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DOI: https://doi.org/10.1038/35002105
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