| First Author | Stoklasek TA | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 11 | Pages | 6857-65 |
| PubMed ID | 21041729 | Mgi Jnum | J:166134 |
| Mgi Id | MGI:4839824 | Doi | 10.4049/jimmunol.1001601 |
| Citation | Stoklasek TA, et al. (2010) MHC Class I and TCR Avidity Control the CD8 T Cell Response to IL-15/IL-15R{alpha} Complex. J Immunol 185(11):6857-65 |
| abstractText | IL-15 operates via a unique mechanism termed transpresentation. In this system, IL-15 produced by one cell type is bound to IL-15Ralpha expressed by the same cell and is presented to apposing cells expressing the IL-15Rbeta/gammaC complex. We have shown that administering soluble IL-15Ralpha complexed with IL-15 can greatly enhance IL-15 activity. We now show that the naive CD8 T cell response to exogenous IL-15/IL-15Ralpha complex is MHC class I dependent. In the absence of beta2 microglobulin, naive CD8 T cells scarcely proliferated in response to IL-15/IL-15Ralpha complex, whereas memory cells proliferated, although to a lesser extent, compared with levels in control mice. The loss of beta2m or FcRn slightly reduced the extended half-life of IL-15/IL-15Ralpha complex, whereas FcRn deficiency only partially reduced the naive CD8 T cell proliferative response to IL-15/IL-15Ralpha complex. In addition, we demonstrated a link between TCR avidity and the ability of a T cell to respond to IL-15/IL-15Ralpha complex. Thus, T cells expressing low-avidity TCR responded poorly to IL-15/IL-15Ralpha complex, which correlated with a poor homeostatic proliferative response to lymphopenia. The inclusion of cognate peptide along with complex resulted in enhanced proliferation, even when TCR avidity was low. IL-15/IL-15Ralpha complex treatment, along with peptide immunization, also enhanced activation and the migratory ability of responding T cells. These data suggest that IL-15/IL-15Ralpha complex has selective effects on Ag-activated CD8 T cells. Our findings have important implications for directing IL-15/IL-15Ralpha complex-based therapy to specific Ag targets and illustrate the possible adjuvant uses of IL-15/IL-15Ralpha complex. |
