Surface T-cell antigen receptor expression and availability for long-term antigenic signaling

It is important to understand how T-cell antigen receptor (TCR) engagement and signaling are regulated throughout an immune response. This review examines the dynamics of surface TCR expression and signaling capacity during thymic and effector T-cell development. Although the TCR can undergo vast changes in surface expression, T cells remain capable of sustaining TCR engagement for long periods of time. This may be achieved by a combination of mechanisms that involve (a) controlling the quantity of surface TCR available for ligand interaction and (b) controlling the quality of surface TCR expression during T-cell activation. TCR signaling itself appears to be one of the main quantitative modulators of surface TCR expression, and it can cause both downregulation and upregulation at different times of T-cell activation. Recent studies indicate that the degree of upregulation is tunable by the strength of antigenic stimulation. There is evidence that qualitatively distinct forms of the TCR exist, and their potential role in sustained antigenic signaling is also discussed. A goal of future studies will be to better characterize these modulations in surface TCR expression and to clarify their impact on the regulation of immune responses.