Molecular signature of human CD8+ T cell with different polyfunctionality in response to different antigen dose (121.8)

Abstract

Abstract T cell polyfunctionality has been shown to be crucial in protective immunity. However, the molecular mechanism controlling CTL polyfunctionality have not yet been determined. Specifically the genetic control linking antigen doses to polyfunctionality has not been explored. In this study, we found that human antigen specific CTL expansion induced by high dose antigenic stimulation is associated with CTL with lower polyfunctionality and higher inhibitory receptors expression, while low does antigen stimulation results in higher T cell polyfunctionality and lower level of inhibitory receptors. Notably, we found that even in an artificial APC system with only signal 1 and signal 2, antigen dose still directly mediated T cell polyfunctionality independent of any inhibitory receptor signaling. The molecular signature associated with optimal CTL polyfunctionality is identified by genomic microarray and these findings are thus important framework for further studies on how to preferentially modulate T cell polyfunctionality.