Tracing and characterization of the low-avidity self-specific T cell repertoire

It is well established that expression of self antigens results in the dele tion of the functional high-avidity self-specific T cell repertoire. Due to the low frequency of naturally occurring low-avidity self-specific T cells , a detailed evaluation of their ability to survive and differentiate into effector and memory populations in vivo has yet to be obtained. We here emp loy tetramer technology to characterize and determine the in vivo fate of a self-specific CD8(+) T cell population specific for a ubiquitously express ed T cell epitope. We find that in influenza nucleoprotein (NP)-transgenic mice (B10NP mice) an oligoclonal population of NP366-374-specific T cells c an be triggered by live influenza virus exposure. The main hallmark of this self-specific T cell population is its diminished avidity for the tetramer ic MHC/NP peptide complex. These low-avidity T cells are not deleted and do not down-regulate their antigen or CD8 receptors, and exhibit cytolytic ac tivity towards tumor cells expressing NP endogenously. Strikingly, a second ary influenza infection generates a typical memory response in the low-avid ity repertoire. The observation that low-avidity T cells persist in vivo an d can differentiate into memory T cells underscores their potential role in anti-tumor immunity.