MHC class Ib–restricted CD8 <sup>+</sup> T cells possess strong tumoricidal activities
Qing Li, Liangyu Lin, Peishun Shou, Keli Liu, Yueqing Xue, Mingyuan Hu, Weifang Ling, Yin Huang, Liming Du, Chunxing Zheng, Xuefeng Wang, Fanjun Zheng, Tao Zhang, Yu Wang, Changshun Shao, Gerry Melino, Yufang Shi, Ying Wang
Abstract
The importance of classical CD8 + T cells in tumor eradication is well acknowledged. However, the anti-tumor activity of MHC (major histocompatibility complex) Ib-restricted CD8 + T (Ib-CD8 + T) cells remains obscure. Here, we show that CX3CR1-expressing Ib-CD8 + T cells (Ib-restricted CD8 + T cells) highly express cytotoxic factors, austerely resist exhaustion, and effectively eliminate various tumors. These Ib-CD8 + T cells can be primed by MHC Ia (MHC class Ia molecules) expressed on various cell types for optimal activation in a Tbet-dependent manner. Importantly, MHC Ia does not allogeneically activate Ib-CD8 + T cells, rather, sensitizes these cells for T cell receptor activation. Such effects were observed when MHC Ia + cells were administered to tumor-bearing K b−/− D b−/− mice. A similar population of tumoricidal CX3CR1 + CD8 + T cells was identified in wild-type mice and melanoma patients. Adoptive transfer of Ib-CD8 + T cells to wild-type mice inhibited tumor progression without damaging normal tissues. Taken together, we demonstrate that MHC class Ia can prime Ib-CD8 + T cells for robust tumoricidal activities.