Cytogenetic location: 14q11.2 Genomic coordinates (GRCh38) : 14:18,200,001-24,100,000
T-lymphocytes recognize antigens via a mechanism that resembles that used by immunoglobulins (Igs; see 147200) produced by B cells. There are 2 main mature T-cell subtypes, those expressing alpha (see TRAC; 186880) and beta (see TRBC1; 186930) chains, and those expressing gamma (see TRGC1; 186970) and delta chains. Unlike secreted Ig molecules, T-cell receptor chains are membrane bound and act through cell-cell contact. Gamma-delta T cells may also recognize antigens directly without presentation by the major histocompatibility complex. The genes encoding the T-cell receptor delta chain are clustered within the T-cell receptor alpha chain locus on chromosome 14. The T-cell receptor delta chain is formed when 1 of 8 variable (V) genes (see 615459), which encode the N-terminal antigen recognition domain, rearranges to at least 1 of 3 diversity (D) gene segments and to 1 of 3 joining (J) gene segments (see 615461) to create a functional V region exon that is transcribed and spliced to a constant region gene (TRDC; 186810) segment encoding the C-terminal portion of the molecule. Unlike other T-cell receptor loci, more than 1 D gene segment may be incorporated into the delta chain, increasing variability. Because the delta locus is located entirely between the V and J segments of the alpha locus, any rearrangement at the alpha locus results in loss of the delta locus. The lymphoid-specific proteins RAG1 (179615) and RAG2 (179616) direct the V(D)J recombination process in both T and B cells. Following synthesis, the gamma and delta chains pair to yield the gamma-delta T-cell receptor heterodimer (Janeway et al., 2005).
Janeway et al. (2005) summarized the germline organization of the human TCR-delta locus, which is located entirely within the TCR-alpha locus. The 3 D gene segments, 3 J gene segments, and single C gene segment of the delta locus lie, in that order, between the V gene cluster and the J gene cluster of the alpha locus. The delta locus contains 8 V gene segments, each preceded by an exon encoding the leader sequence. Two delta V genes are located near the delta C gene, one just upstream of the delta D gene cluster and the other in inverted orientation just downstream of the delta C gene. The other 6 delta V gene segments are interspersed among the alpha V gene segments. Five of these V genes are shared with the alpha locus and can be used by either locus, whereas the other V gene is unique to the delta locus.
Using 'chromosomal walking' techniques and by analysis of a translocation t(8;14)(q24;q11) from a T-cell leukemia, Isobe et al. (1988) mapped the TCR-delta locus within the TCR-alpha locus on chromosome 14q11.2.
Dube et al. (1988) studied the illegitimate recombination that takes place in t(10;14)(q24;q11) in T-cell acute lymphatic leukemia. They identified the first and second D units of the delta gene on the derivative chromosome 10.
Begley et al. (1989) studied a translocation between chromosomes 1 and 14, t(1;14)(p33;q11), in a leukemic stem cell line, DU.528. The translocation resulted in a deletion between the delta chain diversity (D) region genes D(delta1) and D(delta2). The authors described an unusual fusion transcript derived from both chromosomes 1 and 14. They hypothesized that the gene on the chromosome 1 side of the translocation is a locus important for hematopoietic development and oncogenesis, for which they proposed the name SCL (stem cell leukemia); see 187040.
Begley, C. G., Aplan, P. D., Davey, M. P., Nakahara, K., Tchorz, K., Kurtzberg, J., Hershfield, M. S., Haynes, B. F., Cohen, D. I., Waldmann, T. A., Kirsch, I. R. Chromosomal translocation in a human leukemic stem-cell line disrupts the T-cell antigen receptor delta-chain diversity region and results in a previously unreported fusion transcript. Proc. Nat. Acad. Sci. 86: 2031-2035, 1989. [PubMed: 2467296] [Full Text: https://doi.org/10.1073/pnas.86.6.2031]
Dube, I. D., Lu, M., Minden, M. D., Raimondi, S. C., Sutherland, P. M., Beckett, T. A. Breakpoints occur within the delta-chain locus of the T-cell receptor gene in the t(10;14)(q24;q11) of T-cell neoplasia. (Abstract) Am. J. Hum. Genet. 43: A23 only, 1988.
Isobe, M., Russo, G., Haluska, F. G., Croce, C. M. Cloning of the gene encoding the delta-subunit of the human T-cell receptor reveals its physical organization within the alpha-subunit locus and its involvement in chromosome translocations in T-cell malignancy. Proc. Nat. Acad. Sci. 85: 3933-3937, 1988. [PubMed: 2836865] [Full Text: https://doi.org/10.1073/pnas.85.11.3933]
Janeway, C. A., Jr., Travers, P., Walport, M., Shlomchik, M. J. Immunobiology: The Immune System in Health and Disease (6th ed.). New York: Garland Science Publishing , 2005. Pp. 149-154, 164-165.