Molecular mapping of the human T cell receptor gamma (TRG) genes and linkage of the variable and constant regions

Lefranc, Marie‐Paule; Chuchana, Paul; Dariavach, Piona; Nguyen, Catherine; Huck, Sylvie; Brockly, Frédérique; Jordan, Bertrand; Lefranc, Gérard

doi:10.1002/eji.1830190606

Cited by 71 publications

(39 citation statements)

References 30 publications

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“…Also, most contain certain cluster characteristics, such as that of the C region in mammals, where there are at least 4 separate copies of the J-C gene cluster in mice (25), and at least 9 such clusters in human (26). A similar arrangement is also found in the mammalian TCR ␥ and ␤ gene loci (27)(28)(29) and teleost fish light chain genes (24).…”

Section: Discussionmentioning

confidence: 78%

Characterization of arrangement and expression of the T cell receptor γ locus in the sandbar shark

Chen

Kshirsagar

Jensen

et al. 2009

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

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Ig and T cell receptor (TCR) genes consist of separate genomic elements, which must undergo rearrangement and joining before a functional protein can be expressed. Considerable plasticity in the genomic arrangement of these elements has occurred during the evolution of the immune system. In tetrapods, all Ig and TCR chain elements are arranged as translocons. In teleosts, the Ig heavy and TCR chains are translocons, but light chain genes may occur as clusters. However, in chondrichthyes, all of the Ig light and heavy chain genes are arranged as clusters. These clusters vary in number from <10 to several hundred, depending on isotype and species. Here, we report that the germ-line gene for the TCR ␥ chain in a chondrichthyan, the sandbar shark (Carcharhinus plumbeus), is present as a single locus arranged in a classic translocon pattern. Thus, the shark utilizes 2 types of genomic arrangements, the unique cluster organization for Ig genes and the ''conventional'' translocon organization for TCR genes. The TCR ␥ translocon contains at least 5 V region genes, 3 J segment genes, and 1 C segment. As expected, the third hypervariable segment (CDR3), formed by the rearrangement of the V␥ and J␥ segments, contributed the major variability in the intact V region structure. Our data also suggest that diversity may be generated by mutation in the V regions.diversity ͉ translocon M odels proposed for the molecular evolution of the immune system are based on comparative studies of living species. Sharks are critical in this regard, because they belong to an ancient clade (chondrichthyans) that can be traced in the fossil record to the time of the earliest vertebrates. Approximately 450 million years ago, the gnathostomes diverged into 2 groups, the chondrichthyans and the line leading to modern teleosts and tetrapods. It can be concluded that the molecular components of the immune system are ancient and arose before this divergence. This conclusion follows from studies showing that all of the defining elements of the immune system, antibodies, T cell receptors (TCRs), MHC products, and recombination activator genes (RAG), are present in chondrichthyes (1, 2). Thus, continued studies of sharks and rays, the most distant living relatives of mammals with a vertebrate type (VDJ-C recombination) immune system, should provide insights into the molecular origins and evolution of the immune system.A surprising feature of the organization of shark Ig genes was that the V-J-C of light chains (3-5) and V-D-D-J-C of heavy chains (6-8) are arranged in individual clusters. This feature is in contrast to the translocons of higher vertebrates that consist of large arrays of multiple V segments distantly linked to several J and D segments, as well as C domains (9). Although the genes for the TCR chains ␣/␤ and ␥/␦ have been shown to be present in the skate (10) and horned shark (11, 12), the germ-line loci for these molecules have been only partially characterized. Analyses of cDNA sequences in the skate revealed multiple V region families, ...

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Section: Discussionmentioning

confidence: 78%

Characterization of arrangement and expression of the T cell receptor γ locus in the sandbar shark

Chen

Kshirsagar

Jensen

et al. 2009

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

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“…genes. Currently, 14 Vy genes have been identified, 12 of which belong to four subgroups, designated VyI-VylV. The VyI subgroup contains nine genes, consisting of five functional genes (V2, V3, V4, V5 and V8) and four pseudogenes (VI, V5P, V6 and V7) whereas subgroups II, III and IV each contain a single gene, designated V9, VIO and VI1, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…The VyI subgroup contains nine genes, consisting of five functional genes (V2, V3, V4, V5 and V8) and four pseudogenes (VI, V5P, V6 and V7) whereas subgroups II, III and IV each contain a single gene, designated V9, VIO and VI1, respectively. Two pseudogenes, VA and VB, located upstream of V9 and VI1, respectively, belong to none of these groups [14]. The repertoire of TcR Yd genes consists of at least six subfamilies of V5 gene segments, designated NdX-Wdd, each of which contains a single gene [15].…”

Section: Introductionmentioning

confidence: 99%

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Variable gene usage of T cell receptor γ- and δ-chain transcripts expressed in synovia and peripheral blood of patients with rheumatoid arthritis

Olive

Gatenby

Serjeantson

1992

Clinical and Experimental Immunology

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SUMMARY The synovial tissue and fluid of patients with rheumatoid arthritis (RA) contain activated T cells that probably have a central role in the disease process which leads to joint destruction. A subset of T cells, γδ T cells detected at the site of inflammation, may be important in the pathogenesis of the disease. This study investigated variable (V) gene usage of γδ T cell receptors (TcRs) expressed in synovia and peripheral blood of patients with RA by using the polymerase chain reaction (PCR) to amplify TcR γ‐and γ‐chain transcripts. Most patients showed no restriction in Vγ gene usage since synovial mononuclear cells (SMC) expressed TcR γ‐chain transcripts which used the same set of Vγ genes as peripheral blood mononuclear cells (PBMC). In contrast, the majority of patients expressed a restricted SMC Vδ‐chain repertoire biased towards Vδ1, but Vδ2 mRNA transcripts were also detected, albeit at low levels in some patients. The TcR δ‐chain repertoires of PBMC from healthy control subjects were also characterized. There was variation in the TcR δ‐chain repertoires of PBMC from patients when compared with controls, particularly with respect to expression of Vδ4. Vδ4 mRNA transcripts were expressed in PBMC of only two of seven RA patients in contrast with eight of the nine controls (P=0.03). These findings are compatible with reports that γδ T cells in the rheumatoid synovium are reactive to Mycobacterium tuberculosis and that response to M. tuberculosis is restricted to VγL9/Vδ2‐bearing T cells, if a superantigen is involved in the pathogenesis of RA.

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“…The TCR␥ gene is composed of variable (V), joining (J), and constant (C) gene segments that undergo a series of rearrangements to form functionally active genes in mature ␥␦ T-lymphocytes. In the human germline, 14 V␥ gene segments have been identified and divided into four separate subgroups based on sequence homology (4,5). There are five J␥ gene segments organized in two subgroups (J␥1 and J␥2) and two different C␥ genes (C␥1 and C␥2).…”

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confidence: 99%

High expression of a specific T-cell receptor γ transcript in epithelial cells of the prostate

Essand

Vasmatzis

Brinkmann

et al. 1999

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

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We have identified expression of T-cell receptor ␥ chain (TCR␥) mRNA in human prostate and have shown that it originates from epithelial cells of the prostate and not from infiltrating T-lymphocytes. In contrast, the T-cell receptor ␦ chain (TCR␦) gene is silent in human prostate. The major TCR␥ transcript in prostate has a different size than the transcript expressed in thymus, spleen, and blood leukocytes. It is expressed in normal prostate epithelium, adenocarcinoma of the prostate, and the prostatic adenocarcinoma cell line LNCaP. The RNA originates from an unrearranged TCR␥ locus, and it is initiated within the intronic sequence directly upstream of the J␥1.2 gene segment. The prostate-specific TCR␥ transcript consists of the J␥1.2 and C␥1 gene segments, and it has an untranslated sequence including a polyadenylation signal and poly(A) sequence at the 3end. The finding that prostate epithelial cells express a high level of a transcript from a gene that was thought to by exclusively expressed by T-lymphocytes is highly unexpected.

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Molecular mapping of the human T cell receptor gamma (TRG) genes and linkage of the variable and constant regions

Cited by 71 publications

References 30 publications

Characterization of arrangement and expression of the T cell receptor γ locus in the sandbar shark

Characterization of arrangement and expression of the T cell receptor γ locus in the sandbar shark

Variable gene usage of T cell receptor γ- and δ-chain transcripts expressed in synovia and peripheral blood of patients with rheumatoid arthritis

High expression of a specific T-cell receptor γ transcript in epithelial cells of the prostate

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