T Cells and their Receptors

T CELLS AND THEIR RECEPTORS

Each T cell is also committed to a given antigen and recognizes it by one of two TCRs. They may have TCR2s composed of gamma (γ) and delta (δ) chains or TCR2s composed of another heterodimer of alpha (α) and beta (β) chains. These TCR2s are associated with a group of transmem-brance proteins on the CD3 molecule, which takes the antigen recognition sig-nal inside the cell. Signal transduction via the CD3 complex is regulated by a series of kinases, which are associated with the tails of the CD3–TCR complex and regulate phosphorylation. Deficiencies or blocks in the T-cell signaling pathways either atthe cell-surface complex or at the level of the kinases may result in various forms of immunodeficiency. Two other important antigens present on TCR2 cells recognize histocompatibility antigens and will be discussed later. The genes for TCR chains are on different chromosomes with the β and α molecules on chromosome 7, while the α and δ are on chromosome 14. As seen in Figure 1.5, the four chains are made up of a variable region and a constant region similar to those observed with the immu-noglobulins. The variable regions are also numerous and joined at D and J regions by RAG₁ and RAG₂. This permits a diver-sity of antigen recognition similar to that observed with immunoglobulin, but addi-tional somatic mutation is not involved in T cells. These similarities have led to the concept that genes for antigen-specific T cells evolved in the same manner as immu-noglobulin from a parent gene, and both are members of a superantigen family

The TCR complex recognizes small peptides presented to it by the MHC class I and II and depends on the type of T cell.

Figure 1.5 Diagram of the structure of a T-cell receptor.

Helper T cells (CD4) recognize class II anti-gens while suppressor cytotoxic T cells (CD8) recognize class I antigens. Because of the rather low affinity of the reactions, recognition of processed antigen alone is not sufficient to activate T cells. Soluble interleukins are needed to complete the picture and are generated during the anti-gen processing.