Key Concepts of Section 23.5

• The antigen-specific T-cell receptors are dimeric proteins consisting of α and β subunits or γ and δ subunits. T cells occur in at least two major classes defined by their expression of the glycoprotein co-receptors CD4 and CD8 (see Figure 23-29).

• Cells that use class I MHC molecules as the molecular guideposts for antigen recognition (restriction elements, in immunological parlance) carry CD8; those that use class II MHC molecules carry CD4. These classes of T cells are functionally distinct: CD8 T cells are cytotoxic T cells; CD4 T cells provide help to B cells and are an important source of cytokines.

• Genes encoding the TCR subunits are generated by somatic recombination of V and J segments (α chain) and of V, D, and J segments (β chain); their rearrangement obeys the same rules as does rearrangement of Ig genes in B cells (see Figure 23-30). Rearrangement of TCR genes occurs when the lymphocytes are present in the thymus and only in those cells destined to become T lymphocytes.

• A complete T-cell receptor includes not only the α and β subunits responsible for antigen and MHC recognition, but also the accessory subunits referred to as the CD3 complex, which is required for signal transduction. Each subunit of the CD3 complex carries in its cytoplasmic tail one or three ITAM domains; when phosphorylated, these ITAMs recruit adapter proteins involved in signal transduction (see Figure 23-31).

• In the course of T-cell development, the TCR β locus is rearranged first. If that locus encodes a functional β subunit, it is incorporated with the pre-Tα chain into a pre-TCR (see Figure 23-32). Like the pre-BCR, the pre-TCR mediates allelic exclusion, that is, the expression of a functionally rearranged T-cell receptor encoded by only one of the two alleles and proliferation of those cells that successfully underwent TCRβ rearrangement.

• Developing T cells that fail to recognize self-MHC molecules die for lack of survival signals. T cells that interact too strongly with self-peptide–self MHC complexes encountered during development are instructed to die (negative selection); those that have intermediate affinity for self-peptide–self MHC complexes are allowed to mature (positive selection) and are exported from the thymus to the periphery.

• T cells are instructed where to go (cell migration) through chemotactic signals in the form of chemokines. Receptors for chemokines are G protein–coupled receptors that show some promiscuity in terms of their binding of chemokines. The complexity of chemokine–chemokine receptor binding allows precise regulation of leukocyte traffic, both within lymphoid organs and in the periphery.