PerspectiveIMMUNOTHERAPY

Mobilizing unconventional T cells

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Science  18 Oct 2019:
Vol. 366, Issue 6463, pp. 302-303
DOI: 10.1126/science.aay7079

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Summary

The human leukocyte antigen–E (HLAE) molecule is expressed on all nucleated cells and presents self-peptides. The resulting complexes can bind to inhibitory receptors on immune killer cells, including ∼50% of natural killer (NK) cells and a subset (∼5%) of CD8+ cytotoxic T lymphocytes (CTLs). Interruption of this inhibitory axis, which serves as an immune checkpoint, can improve effector functions of both CTLs and NK cells and enhance antitumor activity (1). HLA-E antigen expression can also be used as a mechanism for pathogen-infected cells to avoid being killed by NK cells. However, HLA-E can present peptides from pathogens and tumor cells to so-called unconventional CD8+ T cells, which can then be mobilized to fight the infection or tumor. Recent advances in understanding this dichotomy between unconventional T cell activation and NK cell suppression reveal potential preventive and therapeutic applications in infectious diseases and cancer.

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