There are three main classes of T cells—cytotoxic T cells, helper T cells, and regulatory T cells. When activated, they function as effector cells (see Figure 24–17), each with their own distinct activities. Effector cytotoxic T cells directly kill cells that are infected with a virus or some other intracellular pathogen. Effector helper T cells help stimulate the responses of other immune cells—mainly macrophages, dendritic cells, B cells, and cytotoxic T cells; as we will see, there are a variety of functionally distinct subtypes of helper T cells. Effector regulatory T cells suppress the activity of other immune cells.
In this section, we describe these classes and subclasses of T cells and their respective functions. We discuss how they recognize foreign antigens on the surface of APCs or target cells and the crucial part played by MHC proteins in the recognition process. We begin by considering the cell-surface receptors that T cells use to recognize antigen.
T cell receptors (TCRs), unlike Igs made by B cells, exist only in membrane-bound form. They are composed of two transmembrane, disulfide-linked polypeptide chains, each of which contains two Ig-like domains—one variable and one constant. On most T cells, the TCRs have one α chain and one β chain (Figure 24–32).
The genetic loci that encode the αand β chains are located on different chromosomes. Like an Ig heavy-chain locus (see Figure 24–29), the TCR loci contain separate V, D, and J gene segments (or just V and J gene segments in the case of the α-chain locus), which are brought together by site-specific recombination during T cell development in the thymus. With one exception, T cells use the same mechanisms to generate antigen-binding site diversity of their TCRs as B cells use to generate antigen-binding site diversity of their Igs, and they use the same V(D)J recombinase; thus, humans or mice deficient in this recombinase cannot make functional B or T cells. The mechanism that does not operate in TCR diversification is antigen-driven somatic hypermutation. Thus, the affinities of TCRs tend to be low (Ka ≈ 105–107 liters/mole). Various co-receptors and cell–cell adhesion proteins, however, greatly strengthen the binding of a T cell to an APC or target cell.
Figure 24–32 A T cell receptor (TCR) heterodimer. (A) Schematic drawing showing that the receptor is composed of an α and a β polypeptide chain. each chain has a large extracellular part that is folded into two Ig-like domains—one variable (V) and one constant (c). A Vα and a Vβ domain (shaded in blue) form the antigen-binding site. Unlike Igs, which have two binding sites for antigen, Tcrs have only one. The αβ-heterodimer is noncovalently associated with a large set of invariant membrane-bound proteins (not shown), which help activate the T cell when the Tcrs bind their specific antigen (see Figure 24–45B). A typical T cell has about 30,000 Tcrs on its surface. (B) The three-dimensional structure of the extracellular part of a Tcr. The antigen-binding site is formed by the hypervariable loops of both the Vα and Vβ domains (black), and it is similar in its overall dimensions and geometry to the antigen-binding site of an Ig molecule. (B, based on K.c. Garcia et al., Science 274:209–219, 1996.)