Genomic structure and chromosomal location of the mouse pre-T-cell receptor alpha gene

Abstract

The mouse pre-T-cell receptor alpha (pT alpha) chain is a 33,000 M(r) glycoprotein expressed on the surface of immature thymocytes as a disulfide-linked heterodimer with the T-cell receptor beta (TCR beta) chain, and in association with proteins of the CD3 complex. The cDNA for pT alpha, isolated previously, encodes a type I transmembrane protein that is a member of the immunoglobulin (Ig) superfamily. Here we report the complete nucleotide sequence, the exon/intron structure, and the chromosomal location of the pTa gene. The gene spans about 8.4 kilobases (kb) and consists of four exons. Exon 1 encodes the 5' untranslated region, the leader peptide, and the first three amino acids of the mature protein. This exon is followed by a relatively long intron of 4.9 kb that contains many short interspersed repeats (SINEs) of the B1 and B2 family. The second exon encodes the extracellular Ig-like domain and exon 3 with just 45 base pairs the connecting peptide (CP), including the cysteine required for heterodimer formation. A similar exon/intron structure encoding corresponding parts of the mature polypeptide is found both in the Tcra and Tcrd constant region genes. The last exon encodes the transmembrane portion, the cytoplasmic tail, and about 540 nucleotides of 3' untranslated sequence, including a B2 repetitive element. In situ hybridization maps the pTa gene to the D/E1 region of mouse chromosome 17.

Cloning and comparative analysis of the human pre-T-cell receptor alpha-chain gene.

“…This type of element is known to generate recombination or translocation events by insertional mutagenesis. Moreover, a difference between the gene structure of the murine pTa gene and the TCRa and TCR6 genes is that the pTa transmembrane region, the cytoplasmic tail, and the 3' untranslated region are encoded by a single exon (24), whereas in TCRa and TCR8 genes the 3' untranslated region is encoded by a separate exon. These differences could suggest that the 3' part of the pTa molecule has been subjected to variation.…”

“…Thus, the human pTa gene maps to the 6p21.2-6pl2 region of the human genome. Recently, the murine pTa gene was localized in the D.E1 region of chromosome 17 (24), which is homologous to the short arm of human chromosome 6. Thus, in both human and mouse the pTa gene is localized in the area of the major histocompatibility complex.…”

Identification of the pre–T-cell receptor α chain in nonmammalian vertebrates challenges the structure–function of the molecule

“…These conserved residues are believed to be involved in charged interactions with the transmembrane domain of a component of the CD3 complex (5). In all pTα sequences analyzed, these basic and positively charged residues are always separated by four nonconserved amino acids (Fig.…”

“…PTCRA was identified initially in human and mouse (5,6). The PTCRA transcription unit consists of four exons.…”

MHC‐restricted T cell receptor signaling is required for αβ TCR replacement of the pre T cell receptor

“…To investigate whether the HY-TCR could still ameliorate the developmental block at the b-selection point in the absence of its restricting MHC element, we bred the pTa -/-HY-I model onto the H-2 d background, which does not support positive selection of the HY-TCR [21]. Because the MHC and the pTa gene are located approximately 11 megabases apart on the same chromosome (www.ensembl.org) [22], mice had to be screened for a recombinant harboring the pTa-deficient allele on the same chromosome as H-2 d . To this end, pTa-deficient mice were crossed with BALB/c mice, such that the resulting F1 generation was heterozygous for pTa deficiency and H-2 d/b .…”