T lymphocytes, of which there are several types, develop in the thymus. They are characterized by the type of T-cell receptors they express and by the expression of certain markers. The two main classes of T cells express either a cell-surface protein called CD8 or another called CD4. These are not just random markers, but are important for a T cell’s function, because they help to determine the interactions between the T cell and other cells. Recall from Section 1-10 that T cells detect peptides derived from foreign antigens that are displayed by MHC molecules on a cell’s surface. CD8 and CD4 function in antigen recognition by recognizing different regions of MHC molecules and by being involved in the signaling of the T-cell receptor that is engaged with its antigen. Thus, CD4 and CD8 are known as co-receptors and they provide a functional difference between CD8 and CD4 T cells,
Importantly, there are two main types of MHC molecules, called MHC class I and MHC class II. These have slightly different structures, but both have an elongated groove on the outer surface that can bind a peptide (Fig. 1.29). The peptide becomes trapped in this groove during the synthesis and assembly of the MHC molecule inside the cell, and the peptide:MHC complex is then transported to the cell surface and displayed to T cells (Fig. 1.30). Because CD8 recognizes a region of the MHC class I protein while CD4 recognizes a region of MHC class II protein, the two co-receptors functionally distinguish T cells. Therefore, CD8 T cells selectively recognize peptides that are bound to MHC class I molecules, while CD4 T cells recognize peptides presented by MHC class II.
The most direct action of T cells is cytotoxicity. Cytotoxic T cells are effector T cells that act against cells infected with viruses. Antigens derived from the virus multiplying inside the infected cell are displayed on the cell’s surface, where they are recognized by the antigen receptors of cytotoxic T cells. These T cells can then control the infection by directly killing the infected cell before viral replication is complete and new viruses are released (Fig. 1.31). Cytotoxic T cells carry CD8, and so recognize antigen presented by MHC class I molecules. Because MHC class I molecules are expressed on most cells of the body, they serve as an important mechanism to defend against viral infections.
Fig. 1.29 MHC molecules on the cell surface display peptide fragments of antigens. mHC molecules are membrane proteins whose outer extracellular domains form a cleft in which a peptide fragment is bound. these fragments are derived from proteins degraded inside the cell and include both self and foreign protein antigens. the peptides are bound by the newly synthesized mHC molecule before it reaches the cell surface. there are two kinds of mHC molecules, mHC class I and mHC class II; they have related but distinct structures and functions. Although not shown here for simplicity, both mHC class I and mHC class II molecules are trimers of two protein chains and the bound self or nonself peptide.
Bound peptides transported by MHC class I to the cell surface Viral proteins synthesized in cytosol endoplasmic reticulumcytosol Peptide fragments of viral proteins bound by MHC class I in ER cytosol nucleus Virus infects cell
Fig. 1.30 MHC class I molecules present antigen derived from proteins in the cytosol. In cells infected with viruses, viral proteins are synthesized in the cytosol. Peptide fragments of viral proteins are transported into the endoplasmic reticulum (er), where they are bound by mHC class I molecules, which then deliver the peptides to the cell surface.