Coordinated Vγ and Vδ gene segment rearrangements in human T cell receptor γ/δ+ lymphocytes

Sturm, Els; Braakman, Eric; Bontrop, Ronald E.; Chuchana, Paul; Griend, René J. De Van; Koning, Frits; Lefranc, Marie‐Paule; Bolhuis, R. L. H.

doi:10.1002/eji.1830190717

Cited by 31 publications

(14 citation statements)

References 36 publications

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“…20 representative y/S clones were phenotyped with additional mAbs that react with specific V region-encoded protein products and thus detect functional TCR gene rearrangements. As described for the majority of peripheral blood y /S cells (16), all 20 clones were TiyA+ (reactive with Vy9 [17]) and BB3 + (reactive with V62 [18]). However, all these clones lacked the determinant recognized-by mAb STCS1 (reactive with VS1 [16]) .…”

Section: Resultsmentioning

confidence: 66%

“…As described for the majority of peripheral blood y /S cells (16), all 20 clones were TiyA+ (reactive with Vy9 [17]) and BB3 + (reactive with V62 [18]). However, all these clones lacked the determinant recognized-by mAb STCS1 (reactive with VS1 [16]) . The phenotype of these clones is consistent with the FRCS analysis of this donor's peripheral blood y/S cells that seem BB3+ and TiyA+ , but are STCS1 -.…”

Section: Resultsmentioning

confidence: 66%

“…In contrast to these y/b clones, all TCRa/(3 clones with non-MHCrestricted cytotoxic activity against K562 that were obtained from the same donor (33 clones) did not lyse Daudi or Raji cells, although many clones lysed Molt4 and/or TK6 targets (representative clones shown in Tables III and IV). Phenotypic analysis with mAbs (Tables I, II, IV, and V Figure 1) identified the NK clones as Leu-11a (CD16)' or Leu-11a-and Leu-19 (CD56)+, but TCR61 -while they/b clones were TCRy/b-1+, TCRb1 + (mAbs reactive with ally/b cells [8,16]). Most y/b T cell clones were double negative for CD4 and CD8, but some clones expressed variable levels ofCD8.…”

Section: Resultsmentioning

confidence: 99%

“…Nevertheless, other yet unknown structures distinct from the TCR and these adhesion molecules could be functional in the lytic mechanism used by y/S T cells. Despite the great potential diversity of the TCRy/S (predominantly due to the junctional diversity of the S chain) (1, 2, 30, 31), the number of functional gene combinations utilized by human peripheral y/S T cells appears quite limited (16)(17)(18). The cytotoxicity pattern by the BB3/Ti-yA+ y/S clones was the same when using clones obtained from two additional blood donors and comparing them with NK and a/J3 clones derived from each of these donors (not shown) .…”

Section: Resultsmentioning

confidence: 99%

“…For immunofluorescence studies, cells were labeled with mAbs reactive against CD2 (Leu-5b), CD3 (Leu-4), CD4 (Leu-3a), CD8 (Leu-2b), CD16 (Leu11a), CD56 (Leu-19) epitopes, and TCR a/(3 (WT31) (all from Becton Dickinson & Co., Mountain View, CA) . mAbs reactive with all cells expressing the TCRy/b were TCR 61 (T Cell Sciences, Cambridge, MA) and TCR y/b-1 (8,16) . In addition, some y/6 clones were stained with mAbs that detect specific V region determinants on the TCR y/b.…”

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confidence: 99%

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Gamma/delta T cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatibility complex-restricted cytolysis.

Fisch

Malkovsky

Braakman

et al. 1990

The Journal of Experimental Medicine

159

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Non-MHC-restricted killer cells are cytotoxic lymphocytes that can mediate cytolysis of most tumor targets without apparent selectivity and restriction by the MHC, particularly when activated with IL-2. These effector cells include predominantly NK cells and T cells expressing the TCR-gamma/delta. We found that TCR-gamma/delta-1+, delta TSC1-, BB3+, Ti gamma A+ T cell clones mediate a characteristic cytolytic pattern of non-MHC-restricted cytolysis that is markedly different from NK clones and alpha/beta T cell clones derived from the peripheral blood of the same normal individuals. The characteristic finding is that all BB3/Ti gamma A+ gamma/delta clones mediate strong cytolysis of Daudi cells but they do not lyse Raji cells. In contrast, NK clones from the same donors mediate strong cytolysis of both Daudi and Raji targets. Cytotoxicity by the gamma/delta clones on certain target cells such as Daudi and Molt 4 can be specifically inhibited by mAbs reactive against the TCR-gamma/delta. Therefore, the TCR-gamma/delta on these clones either directly recognizes target epitopes on some tumor targets or it is involved in the regulation of their cytotoxic function. The expression of TCR-gamma/delta products reacting with the BB3 and Ti gamma A mAbs reflects the usage of identical TCR-gamma/delta V region genes that appear to be associated with the characteristic pattern of non-MHC-restricted cytotoxicity displayed by this major subset of human peripheral blood gamma/delta cells.

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Section: Resultsmentioning

confidence: 66%

Section: Resultsmentioning

confidence: 66%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Gamma/delta T cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatibility complex-restricted cytolysis.

Fisch

Malkovsky

Braakman

et al. 1990

The Journal of Experimental Medicine

159

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Selective expansion of t cells bearing the γ/δ receptor and expressing an unusual repertoire in the synovial membrane of patients with rheumatoid arthritis

Andreu

Trujillo

Alonso

et al. 1991

Arthritis & Rheumatism

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In a study of 7 patients with rheumatoid arthritis (RA), we characterized the T cell population present in the synovial membrane, thought to be the location where T cells trigger the disease. Synovial membrane lymphocytes from the RA patients were found to have a selective expansion of γ/δ T cells (8.8% in synovial membrane versus 4% in peripheral blood). Expansion of the γ/δ T cell subset was not found in the synovial membrane of patients with osteoarthritis. We characterized the γ/δ T cell repertoire using monoclonal antibodies TiγA, BB3, and δTCS1, which recognize the gene products encoded by Vγ9, Vδ2, and Vδ1‐Jδ1, respectively. The majority of the synovial γ/δ T cells did not express the repertoire encoded by these genes, which is found in nearly 100% of the peripheral blood γ/δ T cells of healthy volunteer donors and in the thymus at early stages of development. We conclude that the synovial membrane of patients with RA displays a selective expansion of a specific population of γ/δ T cells expressing a clonotypic receptor not yet serologically defined, which might be implicated in the development of the disease.

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γ/δ T cell antigen receptors expressed on tumor‐infiltrating lymphocytes from patients with solid tumors

Nanno¹,

Seki²,

Mathioudakis³

et al. 1992

Eur J Immunol

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The expression of gamma/delta T cell antigen receptors (TcR) in T cell lines or clones derived from tumor-infiltrating lymphocytes (TIL) from patients with solid tumors was investigated. gamma/delta TcR T cell lines were derived from TIL from patients with Wilms tumor, sarcoma or metastatic melanoma by stimulation with autologous tumor cells alone and recombinant interleukin 2 and they exhibited nonspecific cytotoxicity against autologous and allogeneic tumor cells, or cells of the K562 or the MEL21 tumor cell lines. Two T cell lines were derived from a patient with Wilms tumor. One of them expressed a non-disulfide-linked gamma/delta TcR using the 60-kDa gamma chain, whereas, the other expressed a disulfide-linked gamma/delta TcR. A T cell line was derived from a patient with sarcoma and expressed a disulfide-linked gamma/delta TcR, whereas, a T cell line derived from a patient with melanoma expressed a non-disulfide-linked gamma chain of 62 kDa. Several T cell clones were developed from patients with metastatic melanoma or Wilms tumor and expressed either disulfide- or non-disulfide-linked gamma/delta TcR. Northern analysis of RNA from certain of these clones revealed a full-length gamma chain transcript, whereas, the alpha or beta chain transcripts were either absent or truncated. These T cell clones exhibited nonspecific cytotoxicity. Both disulfide- and non-disulfide-linked TIL T cell lines and clones expressed the delta TCS1 determinant. gamma/delta TcR+ cells in freshly prepared TIL from these patients were present in low proportions (less than 5%) and their delta TCS1/delta 1 ratios were within the range observed in the peripheral blood of normal donors. These results demonstrate that both disulfide- and non-disulfide-linked gamma/delta TcR are expressed on T cell lines and clones derived from TIL from solid tumors. Non-disulfide-linked gamma/delta TcR using the 56-66-kDa gamma chain are frequently found on TIL-derived T cell lines and clones. These 56-66-kDa gamma chains are rarely expressed on T cell lines or clones derived from peripheral blood lymphocytes of normal donors.

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Coordinated V_γ and V_δ gene segment rearrangements in human T cell receptor γ/δ⁺ lymphocytes

Cited by 31 publications

References 36 publications

Gamma/delta T cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatibility complex-restricted cytolysis.

Gamma/delta T cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatibility complex-restricted cytolysis.

Selective expansion of t cells bearing the γ/δ receptor and expressing an unusual repertoire in the synovial membrane of patients with rheumatoid arthritis

γ/δ T cell antigen receptors expressed on tumor‐infiltrating lymphocytes from patients with solid tumors

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