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Modulation of TCR-mediated signaling pathway by thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2).

S Saitoh, A Kosugi, S Noda, N Yamamoto, M Ogata, Y Minami, K Miyake and T Hamaoka
J Immunol December 15, 1995, 155 (12) 5574-5581;
S Saitoh
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A Kosugi
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S Noda
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N Yamamoto
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M Ogata
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Y Minami
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K Miyake
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T Hamaoka
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Abstract

Thymic shared antigen-1 (TSA-1) is a glycosyl-phosphatidylinositol (GPI)-anchored differentiation Ag expressed on murine lymphocytes, and is identical to stem cell Ag-2 (Sca-2). Using newly established mAb against TSA-1/Sca-2, we have previously shown that surface TSA-1 expression is induced upon activation in T cells, and that anti-TSA-1 inhibits IL-2 production induced by anti-CD3 stimulation in T cell hybridomas. In the present study, we have analyzed the functional role of TSA-1 during T cell activation using normal T cells, T cell hybridomas, and transfected Jurkat cell lines that expressed either GPI-anchored or transmembrane form of TSA-1. Anti-TSA-1 inhibited IL-2 production from normal T cells stimulated with soluble anti-CD3 plus accessory cells. Anti-TSA-1 exhibited the inhibitory effect on T cells, but not on accessory cells, because anti-TSA-1 inhibited IL-2 production in Jurkat cells transfected with TSA-1 cDNA, but not in control transfectant. A transmembrane form of TSA-1 was expressed in Jurkat cells by fusing the extracellular portion of TSA-1 to the transmembrane and cytoplasmic regions of the class 1 Db. The analysis using this transfectant revealed that anti-TSA-1-mediated inhibition of IL-2 production did not require the GPI anchor of TSA-1. Finally, in addition to the inhibition of IL-2 production, tyrosine phosphorylation of CD3 zeta-chains observed following TCR stimulation, one of the important early activation events, was markedly reduced by anti-TSA-1. These results imply that TSA-1/Sca-2 plays an important regulatory role in the TCR signaling pathway of activated T cells in addition to its role in T cell differentiation.

  • Copyright © 1995 by American Association of Immunologists

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The Journal of Immunology
Vol. 155, Issue 12
15 Dec 1995
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Modulation of TCR-mediated signaling pathway by thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2).
S Saitoh, A Kosugi, S Noda, N Yamamoto, M Ogata, Y Minami, K Miyake, T Hamaoka
The Journal of Immunology December 15, 1995, 155 (12) 5574-5581;

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Modulation of TCR-mediated signaling pathway by thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2).
S Saitoh, A Kosugi, S Noda, N Yamamoto, M Ogata, Y Minami, K Miyake, T Hamaoka
The Journal of Immunology December 15, 1995, 155 (12) 5574-5581;
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Print ISSN 0022-1767        Online ISSN 1550-6606