CD8 T cell response to IL‐15/IL‐15Rα complex is MHC class I dependent

Abstract

Recent findings illustrate that IL‐15 operates via a unique mechanism termed transpresentation. In this system, IL‐15 produced by one cell type is bound to IL‐15Rα expressed by the same cell and presented to apposing cells expressing the IL‐15Rβ/γC complex. We have recently shown that administering soluble IL‐15Rα complexed with IL‐15 can greatly enhance IL‐15 activity by increasing IL‐15 half‐life and forcing transpresentation of IL‐15. Furthermore, IL‐15/IL‐15Rα complex can cause the proliferation and maturation of naïve CD8 T cells. We now show that the CD8 T cell response to exogenous IL‐15/IL‐15Rα complex is MHC class I dependent. In the absence of MHC class I, naïve CD8 T cells scarcely proliferate in response to IL‐15/IL‐15Rα complex. In addition, providing specific peptide along with IL‐15/IL‐15Rα complex can enhance the proliferation of antigen‐specific CD8 T cells. The responding antigen‐specific CD8 T cells undergo an expansion and contraction phase, resulting in a larger frequency of remaining memory‐phenotype cells. These data suggest that IL‐15/IL‐15Rα complex has selective effects on antigen activated CD8 T cells. Our findings have important implications for directing IL‐15/IL‐15Rα complex based therapy to specific antigen targets, and illustrate the possible adjuvant uses of IL‐15/IL‐15Rα complex.NIH Grant AI‐051583 (to L.L.) and NCC Predoctoral Fellowship (to T.A.S.).