Activation of T lymphocytes

T cell activation is an antigen-dependent process leading to proliferation and differentiation of naive T cells into effector cells. This process requires primary and coactivating signals triggering intracellular signal transduction cascades and new gene expression.

Signal 1 occurs when the T cell receptor (TCR) binds a foreign antigenic protein on the cell surface of an antigen-presenting cell (APC) or a target cell, and the T cell coreceptor binds the major histocompatibility complex (MHC) molecule on the APC or target cell (Fig 1).

Signal 2 occurs when co-activating molecules on the T cell bind costimulatory proteins on the APC or target cell, the most important of which is the B7 protein. B7 binding by T cell costimulatory proteins results in T cell activation, whereas a lack of binding results in apoptosis of the cell. Because most native cells do not possess B7, this system prevents T cells from reacting to the host’s own proteins.

The combination of Signals 1 and 2 determines the nature of the T cell’s response to the antigen. Activation of cytotoxic (CD8) T cells via MHC Type I binding results in the direct lysis of target cells, whereas activation of helper (CD4) T cells via MHC Type II binding causes multiple downstream effects including synthesis of important pro-inflammatory molecules (cytokines) such as tumor-necrosis factor; enhancement of antibody secretion by B cells, and enhanced killing by cytotoxic CD8 cells.

CD4 T cells affect a broad range of immune responses, and are therefore critical for normal immune function. As physicians have learned from AIDS patients, in whom CD4 cells are diminished or dysfunctional, the affected host is resultantly susceptible to opportunistic infections. In contrast, when CD4 cells are overactive, they may oversecrete inflammatory cytokines, resulting in inflammatory diseases such as lupus.

Figure 1. Overview of T cell activation. Adapted from Sharma et al. Nature Reviews Cancer 11, 805-812 (November 2011)