T细胞受体
生物
受体
CD8型
细胞生物学
T细胞
人类白细胞抗原
细胞毒性T细胞
免疫学
淋巴因子激活杀伤细胞
自然杀伤性T细胞
白细胞介素21
免疫系统
主要组织相容性复合体
NK-92
NKG2D公司
白细胞介素12
分子生物学
抗原提呈细胞
先天免疫系统
MHC I级
作者
Lucy C. Sullivan,Thi H. O. Nguyen,Christopher M. Harpur,Sanda Stankovic,Abbie Kanagarajah,Marios Koutsakos,Philippa M. Saunders,Zhangying Cai,James A. Gray,Jacqueline M.L. 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
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2021-04-23
被引量:6
标识
DOI:10.1126/sciimmunol.abe9057
摘要
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 inhibitory natural killer cell receptors (NKRs) KIR2DL1 and KIR2DL2/L3. On the other hand, UL40/HLA-E T cells bearing lower-affinity TCRs expressed the activating receptor NKG2C. Activation of T cells bearing higher-affinity TCRs was regulated by the interaction between KIR2D receptors and HLA-C. These findings identify a role for NKR signaling in regulating self/non-self discrimination by HLA-E-restricted T cells, allowing for antiviral responses while avoiding contemporaneous self-reactivity.
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