Non-canonical pre-TCR signaling during T cell development

T cells undergoing maturation in the thymus need to receive a pre-TCR-delivered signal to undergo ¿-selection and develop further properly. The pre-TCR is composed of a constitutively expressed pre-T¿ (pT¿) chain and a de novo expressed TCR¿ chain. A productive recombination of the TCR¿ chain is mandatory to overcome the first checkpoint that controls T cells survival. However, in a very low but consistent extent, thymocytes lacking a canonical pre-TCR can differentiate further. We show that thymocytes lacking a classical pre-TCR can survive and differentiate to later developmental stages. Besides, signaling through a pT¿-less TCR is enough to achieve Ca2+ influx and NF-¿B activation. In addition, we demonstrate that the mechanisms underlying cell death of thymocytes in conditions of proteasome inhibition are in great extent independent of NF-¿B activation and pre-TCR or TCR signaling, and are rather dependent on triggering the pro-apoptotic terminal UPR.