Regional location of T cell receptor gene Ti alpha on human chromosome 14.

Abstract

The human T cell receptor is a molecular complex consisting of a clonotypic, disulfide-linked heterodimer, termed Ti, and three noncovalently associated monomorphic T3 components (1). The Ti molecule that presumably serves as the binding site for nominal antigen and the major histocompatibility complex (MHC) is composed of a 49-54 kilodalton (kD) a subunit and a 43 kD/3 subunit (1). In contrast, the 20-25 kD T3 proteins are likely involved in signal transduction after ligand binding to Ti (1). Sequence analysis at both the protein and DNA level indicates that the Ti o~ and/3 subunits are comprised of immunoglobulin-like domains and that each contains variable, joining, and constant (V, J, C) region encoding segments that rearrange during T lineage ontogeny (1).Recent chromosomal mapping studies (2-4) localized the human T cell receptor/3 chain gene (TiB) to human chromosome 7, although its regional position remains unclear. Here, we demonstrate that human chromosome region 14pter>q21 contains the human Tio~ gene. This is of particular cytogenetic interest, since chromosomal inversions and translocations involving this region have recently been observed in human T cell malignancies (5). Furthermore, the apparent lack of genetic linkage between the Tio~ gene and the IgH cluster in humans can now be explained by the great physical distance between these loci on human chromosome 14. Materials and MethodsCell hybrid analysis (6) and blot hybridization experiments (3, 6) followed established methods except that the electro-eluted insert was labeled by the calf thymus primer protocol (7).Isolation of Tic~ REX cDNA Clones. Based on the previously determined amino acid sequence of the Tia REX subunit, we have synthesized an oligonucleotide of 23 bases in length with a complexity of 256 (1). This oligonucleotide pool was used to screen the previously described REX lambda gtl0 cDNA library (1). Positives were isolated and inserts subcloned in pBR322 (paREX) (8). DNA sequence analysis of paREX indicated that it encoded a portion of the V, J, and C regions of the REX human Tia subunit (~400 nucleotides long).

T cell receptor alpha-, beta-, and gamma-genes in T cell and pre-B cell acute lymphoblastic leukemia.

“…Rearrangements of this locus are readily detected and intermediate (D/J) 1.0 kilobase (kb) and complete (V/D/J) 1.3 kb transcripts can be discerned (13)(14)(15)(16)(17)(18). The a TCR locus is found at 14qI 1 and is particularly prone to interchromosomal recombination in T cell ALLs (19)(20)(21)(22). It consists ofone C, region, an exceptionally long stretch ofJa segments that may contain 50-100 J regions spread over more than 70 kb.…”