TcR α/β
Most T cells express the α/β type of TcR. The genomic organization of the α and β genes is more complicated than that of the immunoglobulin genes. Indeed, although a locus genes are interspersed with genes for the δ TcR (vide infra), α and β genes are rearranged and expressed at different times and on different T lymphocytes.
The smaller α chain is encoded in a gene cluster consisting of ~100 V genes, ~50 J genes (a high number compared to immunoglobulin J genes) and one C gene. The α chains of various binding specificities are generated by a random genetic recombination of one V and one J gene, which are then joined with Cα, by a mechanism analogous to that of the immunoglobulin L chain. The heavier β chain is encoded by ~ 30 V genes, two D genes, >10 J genes and two C genes. The random joining of one of each V, D and J genes and their rearrangement to one C gene is similar to the process described for immunoglobulin genes. Rearranged VJCα and VDJCβ DNA encodes the α and β chain transcripts, respectively.
TcR genes are rearranged as lymphocytes mature in the thymus. Mature T cells, which are released from the thymus, are irreversibly committed to recognize one specific antigenic epitope in complex with self-MHC molecule.
The combinatorial diversity of TcR is greatly increased by junctional diversity, i.e., the variability of the junctions between different VDJ genes. New nucleotide base pairs are often added at the junction. Indeed, the junctional diversity of TcR is several orders of magnitude greater than that of an immunoglobulin gene. On the other hand, rearranged TcR genes are not subject to somatic mutations that contribute significantly to the generation of antibody diversity. The lack of somatic mutations appears to be related to the fact that the α/β T cells always recognize a complex of antigenic fragment with the self MHC molecule. The receptor mutation could divert the specificity towards self molecules.
The smaller α chain is encoded in a gene cluster consisting of ~100 V genes, ~50 J genes (a high number compared to immunoglobulin J genes) and one C gene. The α chains of various binding specificities are generated by a random genetic recombination of one V and one J gene, which are then joined with Cα, by a mechanism analogous to that of the immunoglobulin L chain. The heavier β chain is encoded by ~ 30 V genes, two D genes, >10 J genes and two C genes. The random joining of one of each V, D and J genes and their rearrangement to one C gene is similar to the process described for immunoglobulin genes. Rearranged VJCα and VDJCβ DNA encodes the α and β chain transcripts, respectively.
TcR genes are rearranged as lymphocytes mature in the thymus. Mature T cells, which are released from the thymus, are irreversibly committed to recognize one specific antigenic epitope in complex with self-MHC molecule.