Self-Recognition Primes T Cells

Science's STKE  03 Dec 2002:
Vol. 2002, Issue 161, pp. tw457
DOI: 10.1126/stke.2002.161.tw457

During T cell maturation, T cells must receive appropriate stimulation through activation of the T cell receptor (TCR) by peptides presented in the context of the major histocompatibility complex II (MHC II). Štefanová et al. investigated how T cells reacted if they had been deprived of exposure to self-antigens before exposure to foreign antigens. In both T cells deprived of self-stimulation by culture in vitro and T cells in vivo deprived of stimulation by injection of animals with antibody to MHC II, subsequent responses to foreign antigens on antigen-presenting cells (APCs) were diminished. In vivo, during migration between secondary lymphoid tissues, T cells are temporarily removed from self-antigen exposure, and T cells isolated from the bloodstream had lower levels of phosphorylated TCR and were less sensitive to foreign antigen than were T cells isolated from lymphoid tissues. In situ analysis of TCR distribution showed that the receptor is asymmetrically localized such that the TCR is enriched at the side of the cell apposed to the APC. Self-antigens produce a low level activation of the TCR complex, which is contrary to the inhibition of TCR signaling that occurs in response to TCR antagonists. This difference may be due to the recruitment of the phosphatase SHP-1 in response to antagonists that does not occur in response to self-antigens. The authors propose that self-antigens and positive selection allow the T cells to be primed for interaction with foreign antigens at very low concentrations.

I. Štefanová, J. R. Dofrman, R. N. Germain, Self-recognition promotes the foreign antigen sensitivity of naïve T lymphocytes. Nature 420, 429-434 (2002). [Online Journal]