Research ArticleT CELLS

Natural killer cell receptors regulate responses of HLA-E–restricted T cells

See allHide authors and affiliations

Science Immunology  23 Apr 2021:
Vol. 6, Issue 58, eabe9057
DOI: 10.1126/sciimmunol.abe9057

You are currently viewing the editor's summary.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

NK receptors fine-tune T cells

The danger of autoreactivity lurks when CD8+ T cells specific for a viral peptide–MHC-I complex also have high affinity for a structurally similar self-peptide. Sullivan et al. assessed the self-peptide reactivity of human cytomegalovirus (CMV)–reactive T cells recognizing a viral UL40 peptide bound to HLA-E from 12 healthy CMV seropositive donors. T cells expressing TCRs with the highest affinity for self-peptide/HLA-E displayed the weakest functional responses. This paradoxical response correlated with increased expression of inhibitory NK receptors in the KIR family and decreased expression of the activating NKG2C receptor. These findings identify a mechanism involving calibrated display of NK receptors that enables HLA-E–restricted T cells to preserve their role as antiviral sentinels while avoiding the deleterious consequences associated with excess autoreactivity.

View Full Text

Stay Connected to Science Immunology