All T cells, like B cells, originate in the mammalian bone marrow. However, unlike B cells, T cells mature in the thymus. A mature T cell is characterized by the presence on the plasma membrane of a T cell receptor (TCR), a protein receptor that recognizes and binds to the antigen.

In many ways, TCRs are similar to antibodies on the surface of B cells. For example, TCRs recognize antigens with a specific structure. In addition, there is a great diversity of TCRs that differ from one another, but each T cell has just one type of TCR on its surface. Binding of TCR to an antigen triggers the T cell to divide into clones, resulting in a pool of T cells that are each specific for a given antigen. Finally, like antibodies, the diversity of TCRs among different T cells results from genomic rearrangement of V, D, J, and C gene segments.

However, TCRs are different from antibodies in important ways. First, they are composed of two, rather than four, polypeptide chains (Fig. 43.15). Second, they are not secreted like antibodies, but are always membrane-bound on the T cell surface. Third, the TCR does not recognize an antigen by itself. Instead, it recognizes an antigen in association with proteins that appear on the surface of most mammalian cells and that are encoded by the major histocompatibility complex, or MHC. MHC proteins were first discovered in transplantation biology because it is their presence that leads to acceptance or rejection of transplanted tissues.

The MHC is a cluster of genes present in all mammals that encode proteins on the surface of cells. The MHC is composed of many genes with a high rate of polymorphism, meaning that there is a lot of variation in the gene sequence (and consequently in the protein sequence) among different individuals. In humans and mice, the genes are divided into three classes: Class I genes are expressed on the surface of all nucleated cells; class II genes are expressed on the surface of macrophages, dendritic cells, and B cells; and class III genes encode several proteins of the complement system and proteins involved in inflammation.

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How do helper and cytotoxic T cells recognize and respond to antigens? Let’s consider the activation of helper T cells first (Fig. 43.16). When an antigen enters the body, it may be recognized by an antibody directly or be taken up by antigen-presenting cells. These cells, which include macrophages, dendritic cells, and B cells, take up the antigen and return portions of it to the cell surface bound to MHC class II proteins. Helper T cells recognize processed antigen along with MHC class II proteins by their T cell receptors. When TCR binds to antigen and MHC class II proteins, the helper T cells release cytokines that activate other parts of the immune system, including macrophages, B cells, and cytotoxic T cells.

Cytotoxic T cells also recognize antigen displayed by host cells, but only antigens that are associated with MHC class I proteins (Fig. 43.16). Because class I proteins are present on virtually all cells, cytotoxic T cells recognize and kill any host cell that becomes abnormal in some way. For example, a virus-infected cell often expresses viral antigens with MHC class I proteins on its surface. Cytotoxic T cells recognize the antigen and MHC class I proteins and kill the cell. Tumor cells express novel antigens along with MHC class I proteins, and in some cases may be eliminated by cytotoxic T cells. Table 43.2 summarizes the major features of helper and cytotoxic T cells.

Once activated, T cells divide and form clones of helper or cytotoxic T cells. Some cells of each type are memory cells that provide long-lasting immunity following an initial infection, as in the case of B cells. Also like B cells, T cells can sometimes be activated too strongly. Earlier, we saw how IgE bound to mast cells and basophils can lead to immediate hypersensitivity reactions characteristic of allergies and asthma. The counterpart in T cells is a delayed hypersensitivity reaction, which, as its name suggests, does not begin right away. For example, if you touch poison ivy, your skin will turn red and start itching only after a delay of several hours or days. Delayed hypersensitivity reactions are initiated by helper T cells, which release cytokines that attract macrophages to the site of exposure, which is typically the skin.

Quick Check 4 How does T cell activation differ from B cell activation?