Summary
The stimulation of T cells with foreign or self-antigens plays a central role in the adaptive immune responses to infection and cancer but also in autoimmunity. T cells use a sophisticated molecular machinery to recognize and respond to cognate antigens. On page 1056 of this issue, Zareie et al. (1) examine the productive and unproductive engagement of the T cell receptor (TCR) with antigens by focusing on binding orientation. The polarity of the interaction affects recruitment of key signaling molecules to the TCR. This topology thus constrains T cell immune responses.