CD45-mediated control of TCR tuning in naive and memory CD8+ T cells
Continuous contact with self-major histocompatibility complex (MHC) ligands is essential for survival of naïve T cells but not memory cells. This surprising finding implies that T cell subsets may vary in their relative T-cell receptor (TCR) sensitivity. Here we show that in CD8+T cells TCR sensitivity correlates inversely with levels of CD5, a marker for strong self-MHC reactivity. We also show that TCR sensitivity is lower in memory CD8+ T cells than naïve cells. In both situations, TCR hypo-responsiveness applies only to short-term TCR signalling events and not to proliferation, and correlates directly with increased expression of a phosphatase, CD45 and reciprocal decreased expression of activated LCK. Inhibition by high CD45 on CD8+ T cells may protect against overt TCR auto-MHC reactivity, while enhanced sensitivity to cytokines ensures strong responses to foreign antigens.
|Authors||Cho, JH.; Kim, HO.; Ju, YJ.; Kye, YC.; Lee, GW.; Lee, SW.; Yun, CH.; Bottini, N.; Webster, K.; Goodnow, C.; Surh, CD.; King, C.; Sprent, J.|
|Responsible Garvan Author|
|Publisher Name||Nature Communications|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/27841348|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/13589|