For both helper T cells and cytotoxic T cells, activation is a complex process that requires the interactions of multiple molecules and exposure to cytokines. The T-cell receptor (TCR) is involved in the first step of pathogen epitope recognition during the activation process.
The TCR comes from the same receptor family as the antibodies IgD and IgM, the antigen receptors on the B cell membrane surface, and thus shares common structural elements. Similar to antibodies, the TCR has a variable region and a constant region, and the variable region provides the antigen-binding site. However, the structure of TCR is smaller and less complex than the immunoglobulin molecules. Whereas immunoglobulins have four peptide chains and Y-shaped structures, the TCR consists of just two peptide chains (α and β chains), both of which span the cytoplasmic membrane of the T cell.
TCRs are epitope-specific, and it has been estimated that 25 million T cells with unique epitope-binding TCRs are required to protect an individual against a wide range of microbial pathogens. Because the human genome only contains about 25,000 genes, we know that each specific TCR cannot be encoded by its own set of genes. This raises the question of how such a vast population of T cells with millions of specific TCRs can be achieved. The answer is a process called genetic rearrangement, which occurs in the thymus during the first step of thymic selection.
The genes that code for the variable regions of the TCR are divided into distinct gene segments called variable (V), diversity (D), and joining (J) segments. The genes segments associated with the α chain of the TCR consist 70 or more different Vα segments and 61 different Jα segments. The gene segments associated with the β chain of the TCR consist of 52 different Vβ segments, two different Dβ segments, and 13 different Jβ segments. During the development of the functional TCR in the thymus, genetic rearrangement in a T cell brings together one Vα segment and one Jα segment to code for the variable region of the α chain. Similarly, genetic rearrangement brings one of the Vβ segments together with one of the Dβ segments and one of thetJβ segments to code for the variable region of the β chain. All the possible combinations of rearrangements between different segments of V, D, and J provide the genetic diversity required to produce millions of TCRs with unique epitope-specific variable regions.
Parker, N., Schneegurt, M., Thi Tu, A.-H., Forster, B. M., & Lister, P. (n.d.). Microbiology. Houston, Texas: OpenStax. Access for free at: https://openstax.org/details/books/microbiology