T cell receptors are very similar to antibodies, with similar genetic mechanisms that bring about a similar degree of diversity. For this resource, the most important type of T cell is the alpha beta (aβ) T cell, so called because instead of light and heavy chains it has alpha (α) and beta (β) chains, which are of comparable size and combine to produce an antigen-binding site (see Figure 1.2b). These two separate chains are coded for by different genes (like the heavy and light chains). The whole TCR is roughly the same as the Fab region of an antibody but is bound to the surface of the cell by a transmembrane region.
The TCR is supported at the base by six proteins that collectively make up the CD3 complex – CD3delta (δ), CD3gamma (γ), two CD3epsilon (ε) and two CD3zeta (ζ) chains (see Figure 1.2b). TCR binding to an antigen leads to phosphorylation of tyrosine amino acids in each of the CD3 chains. CD3ζ has the most tyrosines and is therefore the most important protein in mediating signalling. Tyrosine phosphorylation then sets off a cascade of interactions between the CD3 proteins and other molecules, which results in messages being transmitted to the rest of the cell. If conditions are right, these signals lead to T cell activation whereby the cell’s internal machinery changes, turning it into a cell that can change shape, kill a target and replicate.
Surrounding the TCR are other proteins that help it to recognise and bind to the antigen and then transmit signals to the inside of the cell. The broad division of αβ T cells is based on the presence of one of two molecules, CD4 or CD8. T cells that have CD8 are classically known as cytotoxic T cells that can recognise antigens and kill the target cells, whereas CD4 T cells help B cells to make antibodies.
