Molecular basis for pre-TCR-mediated autonomous signaling

The pre-T-cell receptor (pre-TCR) is a multimeric complex composed of a nascent TCRβ chain, an invariant pre-TCRα (pTα) chain and CD3 molecules, and is crucial for early T-cell development. Despite its structural similarity to the mature αβTCR, which requires MHC–antigen for receptor triggering, the pre-TCR is proposed to initiate signals in a ligand-independent manner. However, the molecular mechanism underlying the autonomous signaling is still unclear. Recent studies have revealed that pTα possesses unique characteristics that promote autonomous signaling. In this review, we summarize current data relating to the molecular mechanism underlying the initiation of pre-TCR-mediated autonomous signaling.