Natural killer cell receptors regulate responses of HLA-E-restricted T cells.
Lucy C Sullivan, Thi HO Nguyen, Christopher M Harpur, Sanda Stankovic, Abbie R Kanagarajah, Marios Koutsakos, Philippa M Saunders, Zhangying Cai, James A Gray, Jacqueline ML Widjaja, Jie Lin, Gabriella Pietra, Maria Cristina Mingari, Lorenzo Moretta, Jerome Samir, Fabio Luciani, Glen P Westall, Karl J Malmberg, Katherine Kedzierska, Andrew G Brooks
Science Immunology | Published : 2021
Human cytomegalovirus (CMV) infection can stimulate robust human leukocyte antigen (HLA)-E-restricted CD8+ T cell responses. These T cells recognize a peptide from UL40, which differs by as little as a single methyl group from self-peptides that also bind HLA-E, challenging their capacity to avoid self-reactivity. Unexpectedly, we showed that the UL40/HLA-E T cell receptor (TCR) repertoire included TCRs that had high affinities for HLA-E/self-peptide. However, paradoxically, lower cytokine responses were observed from UL40/HLA-E T cells bearing TCRs with high affinity for HLA-E. RNA sequencing and flow cytometric analysis revealed that these T cells were marked by the expression of inhibitor..View full abstract