Two distinct T-cell receptor alpha-chain transcripts in a rabbit T-cell line: implications for allelic exclusion in T cells.

Marche, Patrice N.; Kindt, Thomas J.

doi:10.1073/pnas.83.7.2190

Cited by 26 publications

(15 citation statements)

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“…By comparison, members of the same V␤ family are often found in different species of mammals (14,31). This difference could simply reflect the longer evolutionary distance separating the branches of teleost species compared with those in mammals.…”

Section: Discussionmentioning

confidence: 99%

Primary Structure and Complementarity-Determining Region (CDR) 3 Spectratyping of Rainbow Trout TCRβ Transcripts Identify Ten Vβ Families with Vβ6 Displaying Unusual CDR2 and Differently Spliced Forms

Boudinot

Boubekeur

Benmansour

2002

The Journal of Immunology

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VDJ rearrangement at the teleost TCRβ locus leads to a highly diverse repertoire of junctions for each VβJβ combination. From a rainbow trout 5′ RACE library of TCRβ transcripts, 47 clones encompassing a full Vβ-Dβ-Jβ-Cβ sequence were selected and analyzed. A similarity analysis of the sequences evidenced 10 Vβ families, of which 6 were not previously described. Immunoscope and sequence analysis of the Vβ-Dβ-Jβ junctions of the new families confirmed that they create a polyclonal and diverse repertoire. Multiple alignments showed that rainbow trout Vβs possess most of the conserved residues typical of Vβ segments. However, this study revealed a high complementarity-determining region 2 (CDR2) and CDR1 length diversity among rainbow trout Vβ families, suggesting that the spatial orientation of the TCR could fluctuate in the TCR/peptide/MHC complex, depending on the Vβ expressed. Among the new Vβ families, Vβ6 displayed the strongest deviance from typical hypervariable CDR1 and CDR2 loops, with an unusually short CDR2. Moreover, the Vβ6 sequence is overall divergent from typical Vβ sequence, raising the question of its functional relevance. Immunoscope experiments identified a Vβ6-Jβ3 junction, which was amplified during the response against viral hemorrhagic septicemia virus, a fish rhabdovirus. Vβ6 seems therefore to be expressed functionally in a selected TCR. However, the shorter Vβ6 transcripts produced through an alternative splicing lack the C′, C″, D, and E strands of the Vβ domain and are probably nonfunctional.

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Section: Discussionmentioning

confidence: 99%

Primary Structure and Complementarity-Determining Region (CDR) 3 Spectratyping of Rainbow Trout TCRβ Transcripts Identify Ten Vβ Families with Vβ6 Displaying Unusual CDR2 and Differently Spliced Forms

Boudinot

Boubekeur

Benmansour

2002

The Journal of Immunology

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“…Polymorphism in V region gene segments was observed with two probes, one derived from a human TCRa cDNA clone Y14 (13) and the other derived from a rabbit TCRa cDNA clone (VJR5) (30). Multiple fragments, including a polymorphic restriction fragment of -1.0 kb, were observed in blots of Taq I-digested DNA samples hybridized with Y14 probe A (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Five polymorphic forms of the VR5 gene were detected in human DNA samples with the VR5 probe, three polymorphic fragments were revealed in Msp I-digested samples and two were revealed in Pvu II-digested samples. No significant homology was found between VR5 and any of the reported human TCRa V gene sequences and it remains to be determined whether the human VR5 homologues correspond to functional genes or to pseudogenes as in the rabbit (17,30).…”

Section: Methodsmentioning

confidence: 99%

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Genetic recombination within the human T-cell receptor alpha-chain gene complex.

Robinson¹,

Kindt²

1987

Proc. Natl. Acad. Sci. U.S.A.

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Genetic analyses of the human T-cell receptor (TCR) alpha-chain genes indicate that recombination events may occur frequently within this gene complex. Examination of the inheritance of restriction fragment length polymorphisms (RFLP) detected by using probes for constant or variable region gene segments made it possible to assign TCR alpha haplotypes to the 16 parents and 43 offspring of eight families studied. A total of six RFLP, three for the constant region and three for variable region gene segments, were examined in the present studies. Most enzyme and probe combinations tested revealed no polymorphism and those finally selected for the study showed limited polymorphism in that only two or, in one case, three allelic forms of the gene were seen. In spite of limited variability at this level, extensive heterogeneity was observed for the combinations of markers present in haplotypes, suggesting that frequent recombination events have occurred. Most strikingly, multiple combinations of RFLP occurring in close proximity of the TCR alpha constant region gene were observed in this study. A high recombination frequency for the TCR alpha gene complex is further supported by the observation that two children, one in each of two families, inherited recombinant TCR alpha haplotypes.

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“…The strikingly evolutionary conserved (between rabbit, human, and mouse) protein kinase phosphorylation sites were revealed in both C␣TCR and C␤TCR ectodomains (Fig. 4C) by analyzing their published (22,23) amino acid sequences. Interestingly, the CKII phosphorylation site in C␤TCR is located in the solvent-exposed insertion absent in C domains of Ig, as indicated in the x-ray crystallographic structure of the TCR ␤ chain (24).…”

Section: Phosphorylation Of 32 P I -Labeled ␣␤Tcr In Normal T Cells Amentioning

confidence: 99%

Phosphorylation of Extracellular Domains of T-Lymphocyte Surface Proteins

Apasov

Smith

Jelonek

et al. 1996

Journal of Biological Chemistry

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The extracellular accumulation of ATP after activation of T-lymphocytes, as well as the presence of ectoprotein kinases in these cells, led us to propose that T cell surface receptors could be regulated through the reversible phosphorylation of their extracellular domains (ectodomains). Here, in a model system, we used T cell transfectants which express T cell antigen receptor chains lacking intracellular and transmembrane protein domains and 32 P i metabolic labeling of cells to definitively demonstrate phosphorylation of ectodomains of T cell surface proteins. We show that ␣␤TCR ectodomains were phosphorylated intracellularly and constitutively on serine and threonine residues and were then expressed on the T cell surface in phosphorylated form. TCR ectodomains also could be phosphorylated at the cell surface when extracellular [␥-32 P]ATP or [␥-32 P]GTP were used as phosphate donors with the same cells. Consensus phosphorylation sites for serine and threonine protein kinases were found to be strongly evolutionary conserved in both ␣ and ␤ TCR chains constant regions. These results are consistent with the hypothesis, where T cell surface proteins which are phosphorylated intracellularly on their ectodomains, could subsequently be expressed at the cell surface and then be reversibly modified by ectoprotein phosphatase(s) and by ectokinase(s). Such modifications may change T cells cognate interactions by, e.g. affecting TCR-multimolecular complex formation and antigen binding affinity. It is suggested that ␣␤TCR ectodomain phosphorylation could serve as a potential mechanism for regulation of ␣␤TCR-mediated T-lymphocytes response.T cell differentiation and effector functions involve multiple cell-cell contacts and interactions that are mediated by cell surface-located recognition structures, cell adhesion molecules, and growth factor receptors. Recognition of antigenic peptides/ MHC 1 class I and II complexes is the function of extracellular variable regions of the ␣␤ T cell receptor (␣␤TCR), while cytoplasmic domains of ␣␤TCR⅐CD3 complex molecules are considered critical for transmembrane signaling (1, 2).In addition, extracellular domains of cell surface proteins are involved in multimolecular complex formation as underscored by studies of TCR/CD3 subunit assembly (3) and of CD4-TCR interactions that contribute to TCR recognition of MHC class II-presented peptides (4). It was also demonstrated recently that CD45 ectodomains regulate CD4-␣␤TCR associations (5).These considerations and our earlier studies of the role of extracellular ATP in T cell effector functions (6) led us to propose that properties of T cell surface receptors, including cell adhesion proteins and recognition molecules, could be regulated through phosphorylation of their extracellular domains (7, 8) in a manner now accepted as a mechanism for regulation of enzyme-substrate interactions (9).The precedent for such a mechanism was recently provided by studies of CD36 on the platelets surface. It was demonstrated that the specificity of that rec...

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Two distinct T-cell receptor alpha-chain transcripts in a rabbit T-cell line: implications for allelic exclusion in T cells.

Cited by 26 publications

References 43 publications

Primary Structure and Complementarity-Determining Region (CDR) 3 Spectratyping of Rainbow Trout TCRβ Transcripts Identify Ten Vβ Families with Vβ6 Displaying Unusual CDR2 and Differently Spliced Forms

Primary Structure and Complementarity-Determining Region (CDR) 3 Spectratyping of Rainbow Trout TCRβ Transcripts Identify Ten Vβ Families with Vβ6 Displaying Unusual CDR2 and Differently Spliced Forms

Genetic recombination within the human T-cell receptor alpha-chain gene complex.

Phosphorylation of Extracellular Domains of T-Lymphocyte Surface Proteins

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