MHC molecules display short fragments of digested foreign proteins on the surface of cells. These proteins bind to MHC molecules inside the cell and are then transported to the cell
FIGURE 14.3 • Schematic diagram of the molecular structure of the CD3– TCR complex. The CD3 molecule consists of five different polypeptide chains with molecular weights ranging from 16 to 28 kilodaltons. This molecule is closely associated with the T-cell receptor (TCR), which has two polypeptide chains ( and ). The T cell may be activated after the interaction of the TCR with antigen (Ag) displayed on the surface of a major histocompatability complex (MHC) molecule. This interaction transmits the signals to the interior of the cell through the CD3 molecule. This signal stimulates the T cell to secrete interleukins, which in turn stimulate T cells to divide and differentiate.
surface. MHC I and MHC II molecules are products of a “supergene” located on chromosome 6 in humans known as the major histocompatibility gene complex. The expression of this gene complex produces molecules that are specific not only to the individual cell that produces them but also to the tissue type and degree of cellular differentiation.
MHC I is expressed on the surface of all nucleated cells and platelets. MHC I molecules act as a target to allow the elimination of abnormal host cells (e.g., virus-infected or transformed cancer cells). MHC I molecules perform this function by displaying on their surface short fragments of all peptides that are actively synthesized by the cell. Therefore, all endogenous “self ” peptides are displayed on the surface of every cell in the body, but viral or cancer-specific peptides are displayed only on the surface of infected or transformed cells (Fig. 14.4). The MHC I molecules present peptides fragments to cytotoxic CD8 T lymphocytes.
MHC II is limited in its distribution (see Fig. 14.4). It is expressed on the surface of all APCs and is critical in immune interactions. The MHC II molecules present partially digested, endocytosed foreign peptides to helper CD4 T lymphocytes.
Activation of T and B Cells
Activation of T cells requires the presence of costimulatory signals.
become fully activated and to subsequently differentiate and proliferate. The interaction of the TCR and the CD4 or CD8 molecules with the antigen–MHC complex is referred to as a first signal. The second signal, which is called the costimulatory signal, is delivered by the interaction of membrane molecules on T cells and molecules on the APC. The most important interactions are between the CD28 molecule expressed on the T-cell membrane and the B7 (CD86) molecule expressed on the APC membrane. Another pair of costimulatory signals is generated by the interaction of CD40 (on APC cells) with CD40L (CD154), on T cells.
When a helper (CD4) T lymphocyte recognizes an antigen bound to an MHC molecule, the TCR attaches to the antigen–MHC II complex. The binding of the TCR to the antigen–MHC II complex in the presence of a costimulatory signal (derived from the CD28–B7 interaction) activates the helper T lymphocyte to release immune chemicals, or cytokines. Cytokines are immune substances (proteins) that are biologic modulators of immune responses. The specific cytokines  secreted by helper CD4 T lymphocytes are called interleukins (ILs). Interleukins stimulate other T cells, B cells, and NK cells to differentiate and proliferate.
When a cytotoxic CD8 T lymphocyte (CTL) recognizes an antigen–MHC I complex, the TCR attaches to it. If a costimulatory signal is present (derived from the interaction of CD40 and CD40L), the CTL is activated. Once activated,