Disease relevance of Tcra

• T cell receptor alpha chain-deficient (TCR-alpha(-/-)) mice are known to spontaneously develop inflammatory bowel disease (IBD) [1].
• Atm-deficient mice die of malignant thymic lymphomas characterized by translocations within the Tcr alpha/delta locus, suggesting that tumorigenesis is secondary to aberrant responses to double-stranded DNA (dsDNA) breaks that occur during RAG-dependent V(D)J recombination [2].
• Thymic lymphomas that developed in Rag2(-/-) Atm(-/-) mice contained multiple chromosomal abnormalities, but none of these involved the Tcr alpha/delta locus [2].
• Susceptibility to Coxsackievirus B3-induced chronic myocarditis maps near the murine Tcr alpha and Myhc alpha loci on chromosome 14 [3].
• Forbidden CD4(+)betabeta T cells, which produce interleukin (IL)-4 predominantly, are a pathological subset in the development of colitis in T-cell receptor alpha chain (TCRalpha)-deficient mice [4].

High impact information on Tcra

• CD1d is a major histocompatibility complex (MHC) class I-related molecule that functions in glycolipid antigen presentation to distinct subsets of T cells that express natural killer receptors and an invariant T-cell receptor-alpha chain (invariant NKT cells) [5].
• In T-cell precursors, the T-cell-receptor beta chain is expressed before the T-cell-receptor alpha chain and is sufficient to advance T-cell development in the absence of T-cell receptor alpha chains [6].
• Isolation of an excision product of T-cell receptor alpha-chain gene rearrangements [7].
• Of the 56 clones we analysed, nine contained sequences homologous to T-cell receptor alpha-chain joining (J alpha) segments [7].
• The gene encoding the T-cell receptor alpha-chain maps close to the Np-2 locus on mouse chromosome 14 [8].

Chemical compound and disease context of Tcra

• Susceptibility of T cell receptor-alpha chain knock-out mice to ultraviolet B light and fluorouracil: a novel model for drug-induced cutaneous lupus erythematosus [9].
• A vesicular stomatitis virus glycoprotein-specific, class II restricted, CD4+ T-cell clone was obtained and the unidentified T-cell receptor alpha chain cloned in order to establish a T-cell receptor (TCR) alpha chain transgenic mouse line [10].

Biological context of Tcra

• We propose that the array of V alpha genes in various Tcra haplotypes exerts influence over the proportion of CD4 and CD8 subsets generated and may account in part for the observed thymic skewing [11].
• Here, we have shown that polymorphism in CD4/CD8 skewing between B6 and BALB/c mice is determined by the stem cell genotype and not by environmental effects, and that it maps in or near the TCR alpha-chain complex, Tcra [11].
• The resulting congenic line, B10.D2.C-Tcraa/Bo carries a recombination between the Tcra and the hr loci; thus, the transferred differential segment is the centromeric 18-27 cM of the BALB/c chromosome 14 [12].
• Recent studies have demonstrated that the diversity of T-cell receptor alpha (Tcra) gene expression may be confined by a developmental program for gene rearrangement [13].
• RFLP analysis of the Rib-1 locus, located in close proximity to the Tcra locus on chromosome 14, showed that B10.A(18R) carries the Rib-1b allele from B10 [14].

Anatomical context of Tcra

• Assembly of the gene encoding T cell receptor alpha (Tcra) is characterized by an orderly progression of primary and secondary V(alpha)-to-J(alpha) recombination events across the J(alpha) array, but the targeting mechanisms responsible for this progression are mostly unknown [15].
• The mouse Supt16h/Fact140 gene, encoding part of the FACT chromatin transcription complex, maps close to Tcra and is highly expressed in thymus [16].
• Using the human cell line SUP-T1, bearing the inversion inv(14) (q11;q32), we further demonstrated the loci order in man to be centromere-NP-1-Tcr alpha-CTLA-1 [17].
• The effect of the Tcra haplotype on V alpha 2 epitope expression was evident not only among lymph node T cells but also among mature, cortisone-resistant thymocytes [18].
• Segregation analysis of somatic cell hybrids demonstrates that in both patients the breakpoints occur between the variable (V) and constant (C) region genes of the T-cell receptor alpha-chain locus, resulting in the translocation of the C-region gene from chromosome 14 to chromosome 11 [19].

Associations of Tcra with chemical compounds

• Proximity of the CTLA-1 serine esterase and Tcr alpha loci in mouse and man [17].
• Influence of the NH2-terminal amino acid of the T cell receptor alpha chain on major histocompatibility complex (MHC) class II + peptide recognition [20].
• Sequence analysis of the rearranged T-cell receptor alpha chain gene segments from an influenza reactive T-cell clone T2.5-5 and a hemin chloride reactive T-cell hybrid SJL-HE-1.1 have revealed a previously undescribed V alpha gene family [21].

Physical interactions of Tcra

• Major histocompatibility complex determinants select T-cell receptor alpha chain variable region dominance in a peptide-specific response [22].

Regulatory relationships of Tcra

• T cell receptor alpha-chain influences reactivity to Mls-1 in V beta 8.1 transgenic mice [23].

Other interactions of Tcra

• One of these haplotypes (Tcre alpha) appears to arise from a recombination between the Tcrb alpha and Tcra alpha haplotypes, the latter being the most frequently found in the conventional inbred strains [24].
• A similar exon/intron structure encoding corresponding parts of the mature polypeptide is found both in the Tcra and Tcrd constant region genes [25].
• The distribution of the genes along the Tcra locus, plus their structural organization, indicates that successive duplications occurred during the processes of expansion and contraction of the Tcra-V gene subfamilies [26].
• Two genes, Np-1 and Tcra, which fail to recombine in crosses involving conventional strains of mice, were shown to recombine readily in interspecific crosses involving Mus spretus [27].
• Alteration of interleukin 4 production results in the inhibition of T helper type 2 cell-dominated inflammatory bowel disease in T cell receptor alpha chain-deficient mice [1].

Analytical, diagnostic and therapeutic context of Tcra

• Our new approach is based on comparing by flow cytometry the percentage of cells that express a given Valpha-chain between wild-type mice and mice that are hemizygous for a disrupted Tcra locus (Tcra+/-) and consequently unable to express two rearranged Tcra genes [28].
• In man, the human homologue of CTLA-1 was shown by in situ hybridization to map on chromosome 14, at 14q11-q12, where Tcr alpha also maps [17].
• Genomic Southern blot analyses using a rabbit constant region of the T-cell receptor alpha-chain probe revealed the presence of a single constant region gene [29].
• Antigen-specific immunoregulatory activity of a T cell receptor alpha chain generated by expression PCR [30].

References