A large number of signalling motifs in the receptor complex expressed on the surface of T lymphocytes helps prevent autoimmunity, according to a study published online this week in Nature Immunology. As auto-aggressive T lymphocytes can attack healthy tissues and thereby exacerbate many autoimmune diseases, understanding the mechanisms regulating the activity of this cell type is important.
Compared to other immune cells, T lymphocytes contain the highest number?10?of these signalling motifs, called ITAMs, which are required for transmission of intracellular signals. Using a complex genetic manipulation strategy, Dario Vignali and co-workers generated a panel of mice expressing various numbers of functional ITAMs on T lymphocytes. Mice with less than seven functional ITAMs suffered from lethal autoimmune disease precipitated by impaired deletion of self-reactive auto-aggressive T lymphocytes. In general, T lymphocyte development required high numbers of ITAMs, whereas mature T lymphocyte function required lower numbers of ITAMs.
The molecular basis for these different ITAM ‘thresholds’ remains to be understood.