Down-regulation of the T cell receptor by a mitogenic anti-Thy-1 antibody.

Antigen-specific unresponsiveness lasting at least 2 weeks can be induced in a T cell clone by 24-h pretreatment with mitogenic anti-T cell receptor antibodies. In this report the relationship is explored between the antigen-specific unresponsiveness and activation pathways triggered via the T cell receptor and Thy-1: the latter pathway is dependent on the former. A mitogenic anti-Thy-1 antibody (KT16) made the T cell clone unresponsive to specific antigen and to an anti-T cell receptor antibody coupled to Sepharose. The unresponsiveness lasted for at least 7 days. However, cells made unresponsive to specific antigen in these ways (the T cell receptor and Thy-1) could be activated by both interleukin 2 and KT16. KT16 down-modulated the T cell receptor immediately after the pretreatment, but not on day 7 after the pretreatment. These facts indicate that the state of the unresponsiveness was caused by blocking transduction of an activation signal triggered by the T cell receptor to an activation pathway shared by the T cell receptor and Thy-1.