T-cell receptor alpha chain plays a critical role in antigen-specific suppressor cell function.

Kuchroo, Vijay K.; Byrne, Michael C.; Atsumi, Y; Greenfield, Edward; Connolly, Jane B.; Whitters, Matthew J.; O'Hara, R M; Collins, Mary; Dorf, Martin E.

doi:10.1073/pnas.88.19.8700

Cited by 44 publications

(15 citation statements)

References 31 publications

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“…2). These findings may explain previous observations by other investigators that TCRB-expression variants of hapten-or peptide-specific Ts hybridomas do not express TCR, but could release TsF activity (8,25).…”

Section: Discussionsupporting

confidence: 77%

“…It was also found that antisense oligonucleotide corresponding to TCR Va prevented the formation of TsF activity by a Ts hybridoma (7). Kuchroo et al (8,9) developed a series of TCRa-expression variants of Ts hybridomas, and demonstrated that transfection of TCRa cDNA from one Ts hybridoma into the TCRa-f3+ clone of another Ts hybridoma resulted in the formation of TsF activity of the former. These results collectively suggest that a product of TCRa cDNA is TsF or its subunit.…”

mentioning

confidence: 99%

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Cellular mechanisms for the formation of a soluble form derivative of T-cell receptor alpha chain by suppressor T cells.

Ishii

Nakano

Ishizaka³

1996

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

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Upon stimulation with anti-CD3, suppressor T-cell (Ts) hybridomas and homologous transfectants of T-cell receptor ai (TCRa) cDNA in the T-cell hybridoma formed a 55-kDa TCRa chain derivative that bound both the monoclonal anti-TCRa chain and polyclonal antibodies against glycosylation inhibiting factor (GIF). The peptide is a subunit of antigen-specific suppressor T-cell factor (TsF), and is considered to be a posttranslationally-formed conjugate of TCRa chain with GIF peptide. The TCRa derivative is synthesized by the transfectant after stimulation with anti-CD3, and not derived from TCR present on the cell surface. Stimulation of the stable homologous transfectants with anti-CD3 induced translocation of the 13-kDa GIF peptide into endoplasmic reticulum (ER). When a helper Ts hybridoma or a stable transfectant of the same TCRa cDNA in a helper cell-derived TCRai-clone was stimulated with anti-CD3, translocation of GIF peptide was not detected, and these cells failed to secrete a TCRa derivative. However, further transfection of a chimeric cDNA encoding a procalcitonin-GIF fusion protein into the helper cell-derived stable transfectant ofTCRai cDNA resulted in translocation of the GIF protein and formation of bioactive 55-kDa GIF. The results indicated that translocation of GIF peptide through ER is unique for Ts cells, and that this process is essential for the formation/secretion of the soluble form derivative of TCRa chain by T cells.Numerous investigators have described that antigen-specific suppressor T cells (Ts) produce soluble factors that have affinity for homologous antigen and suppress the immune response in antigen-specific manner (reviewed in refs. 1 and 2); however, little was known about the biochemical properties of the suppressor T-cell factors (TsF). In the past 5 years, however, evidence for a possible relationship between TsF and T-cell receptor (TCR) has accumulated. The monoclonal antibody (mAb) specific for the constant region of TCRa chain, H28-710, bound TsF activity from various Ts hybridomas and Ts clones (3-6). It was also found that antisense oligonucleotide corresponding to TCR Va prevented the formation of TsF activity by a Ts hybridoma (7). Kuchroo et al. (8,9) developed a series of TCRa-expression variants of Ts hybridomas, and demonstrated that transfection of TCRa cDNA from one Ts hybridoma into the TCRa-f3+ clone of another Ts hybridoma resulted in the formation of TsF activity of the former. These results collectively suggest that a product of TCRa cDNA is TsF or its subunit.Independent work in our laboratory has shown that ovalbumin-specific Ts hybridomas and bee vemon phospholipase A2-specific Ts hybridomas constitutively secrete a 13-kDa cytokine, designated glycosylation inhibiting factor (GIF), but the same cells produce GIF having affinity for homologous antigen upon antigenic stimulation or crosslinking of TCR/ CD3 (3, 10). The antigen-specific GIF suppressed in vivo antibody responses of syngeneic mice in a carrier-specific manner, indicating that the factor r...

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Section: Discussionsupporting

confidence: 77%

mentioning

confidence: 99%

Cellular mechanisms for the formation of a soluble form derivative of T-cell receptor alpha chain by suppressor T cells.

Ishii

Nakano

Ishizaka³

1996

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

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“…This would help explain the development of colitis in TCR ␣-chain-deficient mice (36, 37), as well as in other TCR Tg mice backcrossed onto RAG-2-deficient mice (34,38,39). Loss of the TCR ␣-chain was associated with the concomitant loss of suppressor activity of Ag-specific T suppressor cell lines (40).…”

Section: Discussionmentioning

confidence: 99%

Expression of Dual TCR on DO11.10 T Cells Allows for Ovalbumin-Induced Oral Tolerance to Prevent T Cell-Mediated Colitis Directed against Unrelated Enteric Bacterial Antigens

Zhou¹,

Borojevic²,

Streutker³

et al. 2004

The Journal of Immunology

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The triggering Ag for inflammatory bowel disease and animal models of colitis is not known, but may include gut flora. Feeding OVA to DO11.10 mice with OVA-specific transgenic (Tg) TCR generates Ag-specific immunoregulatory CD4+ T cells (Treg) cells. We examined the ability of oral Ag-induced Treg cells to suppress T cell-mediated colitis in mice. SCID-bg mice given DO11.10 CD4+CD45RBhigh T cells developed colitis, and cotransferring DO11.10 CD45RBlowCD4+ T cells prevented CD4+CD45RBhigh T cell-induced colitis in the absence of OVA. The induction and prevention of disease by DO11.10 CD4+ T cell subsets were associated with an increase in endogenous TCRα chain expression on Tg T cells. Feeding OVA to SCID-bg mice reconstituted with DO11.10 CD4+CD45RBhigh attenuated the colitis in association with increased TGF-β and IL-10 secretion, and decreased proliferative responses to both OVA and cecal bacteria Ag. OVA feeding also attenuated colitis in SCID-bg mice reconstituted with a mix of BALB/c and DO11.10 CD45RBhigh T cells, suggesting that OVA-induced Treg cells suppressed BALB/c effector cells. The expression of endogenous non-Tg TCR allowed for DO11.10-derived T cells to respond to enteric flora Ag. Furthermore, feeding OVA-induced Treg cells prevented colitis by inducing tolerance in both OVA-reactive and non-OVA-reactive T cells and by inducing Ag-nonspecific Treg cells. Such a mechanism might allow for Ag-nonspecific modulation of intestinal inflammation in inflammatory bowel disease.

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“…In the past several years though, investigators working in several distinct antigenic systems have unequivocally demonstrated the presence of conventional ac3 TCR on Ts hybridomas and clones (23,56,59). Recent studies strongly support a longstanding hypothesis that these suppressor factors are comprised, at least in part, of conventional TCR polypeptides (21,22,24,59). These findings have rekindled an interest in exploring the potential of antigen-specific immunosuppression for the therapy of autoimmune disease and transplant rejection.…”

Section: Discussionmentioning

confidence: 78%

“…These CD8+ Ts cells (Ts2), or soluble proteins secreted by Ts2 cells (TsF2), directly inhibit the function of bulk populations of tubular antigen-specific CD8+ effector cells through a noncytotoxic mechanism ( 18,19). While the molecular definition of suppressor factors is still controver-sial, increasing evidence supports their being closely related to conventional TCR chains (21)(22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of murine nephritogenic effector T cells by a clone-specific suppressor factor.

Meyers

Kelly²

1994

J. Clin. Invest.

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T-cell receptor alpha chain plays a critical role in antigen-specific suppressor cell function.

Abstract: Antigen-specific suppressor T-ceil hybridomas release soluble suppressor factors (TsF) in the supernatant that modulate both in vivo delayed-type hypersensitivity and in vitro plaque-forming cell responses in an antigen-specific manner.

Cited by 44 publications

References 31 publications

Cellular mechanisms for the formation of a soluble form derivative of T-cell receptor alpha chain by suppressor T cells.

Cellular mechanisms for the formation of a soluble form derivative of T-cell receptor alpha chain by suppressor T cells.

Expression of Dual TCR on DO11.10 T Cells Allows for Ovalbumin-Induced Oral Tolerance to Prevent T Cell-Mediated Colitis Directed against Unrelated Enteric Bacterial Antigens

Inhibition of murine nephritogenic effector T cells by a clone-specific suppressor factor.

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