Role of Ly-6A/E and T cell receptor-ζ for IL-2 production: Phosphatidylinositol-anchored Ly-6A/E antagonizes T cell receptor-mediated IL-2 production by a ζ-independent pathway

Elaine K. Codias, Tony J. Fleming, Charles M. Zacharchuk, Jonathan D. Ashwell, Thomas Malek

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Abstract

Ly-6A/E molecules were originally implicated in regulation of T cell activation because anti-Ly-6A/E mAb induce IL-2 production. More recently we have shown that anti-Ly-6A/E also inhibits IL-2 production induced by anti-CD3. In the present study we used mutant and transfected cell lines that varied in expression of Ly-6A/E or TCR-ζ to test whether the positive and negative modulations of IL-2 production by anti-Ly-6A/E occur by distinct mechanisms. Anti-Ly-6A/E inhibited anti-CD3-induced IL-2 production for Ly-6E.1-transfected EL4J cells, but did not affect IL-2 production of the parental Ly-6A/ E-negative EL4J cells. These results indicate that TCR-mediated IL-2 production can occur in the absence of Ly-6A/E expression and establish that anti-Ly-6A/E-induced inhibition of IL-2 production was the result of antibody binding to Ly-6A/E. As expected, MA5.8 (ζ-negative) or CT108 (ζ-truncated) variants of the 2B4.11 T cell hybridoma did not produce IL-2 when stimulated with anti-Thy-1 or anti-Ly-6A/E mAb. In contrast, anti-Ly-6A/E inhibited anti-CD3-induced IL-2 production by MA5.8 and CT108. Furthermore, anti-Ly-6A/E-induced IL-2 production was restored for ζ-transfected MA5.8. Thus, although induction of IL-2 by anti-Ly-6A/E depends on ζ expression, inhibition of IL-2 by anti-Ly-6A/E occurs by a ζ-independent mechanism. Interestingly, anti-Ly-6A/E, but not anti-Thy-1, inhibited anti-CD3-induced IL-2 production by MA5.8 and Ly-6E.1-transfected EL4J. Therefore, inhibition of IL-2 production by anti-Ly-6A/E was not a general property of a mAb binding to a phosphatidylinositol-linked molecule, as has been suggested for induction of IL-2 production. Taken together these data suggest that the molecular mechanisms of induction and inhibition of IL-2 production by anti-Ly6A/E are separable and expression of TCR-ζ is one variable that distinguishes these two pathways.

Original languageEnglish
Pages (from-to)1825-1832
Number of pages8
JournalJournal of Immunology
Volume149
Issue number6
StatePublished - Sep 15 1992

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T-Cell Antigen Receptor
Phosphatidylinositols
Interleukin-2
T-Lymphocytes
Hybridomas

ASJC Scopus subject areas

  • Immunology

Cite this

Role of Ly-6A/E and T cell receptor-ζ for IL-2 production : Phosphatidylinositol-anchored Ly-6A/E antagonizes T cell receptor-mediated IL-2 production by a ζ-independent pathway. / Codias, Elaine K.; Fleming, Tony J.; Zacharchuk, Charles M.; Ashwell, Jonathan D.; Malek, Thomas.

In: Journal of Immunology, Vol. 149, No. 6, 15.09.1992, p. 1825-1832.

Research output: Contribution to journalArticle

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title = "Role of Ly-6A/E and T cell receptor-ζ for IL-2 production: Phosphatidylinositol-anchored Ly-6A/E antagonizes T cell receptor-mediated IL-2 production by a ζ-independent pathway",
abstract = "Ly-6A/E molecules were originally implicated in regulation of T cell activation because anti-Ly-6A/E mAb induce IL-2 production. More recently we have shown that anti-Ly-6A/E also inhibits IL-2 production induced by anti-CD3. In the present study we used mutant and transfected cell lines that varied in expression of Ly-6A/E or TCR-ζ to test whether the positive and negative modulations of IL-2 production by anti-Ly-6A/E occur by distinct mechanisms. Anti-Ly-6A/E inhibited anti-CD3-induced IL-2 production for Ly-6E.1-transfected EL4J cells, but did not affect IL-2 production of the parental Ly-6A/ E-negative EL4J cells. These results indicate that TCR-mediated IL-2 production can occur in the absence of Ly-6A/E expression and establish that anti-Ly-6A/E-induced inhibition of IL-2 production was the result of antibody binding to Ly-6A/E. As expected, MA5.8 (ζ-negative) or CT108 (ζ-truncated) variants of the 2B4.11 T cell hybridoma did not produce IL-2 when stimulated with anti-Thy-1 or anti-Ly-6A/E mAb. In contrast, anti-Ly-6A/E inhibited anti-CD3-induced IL-2 production by MA5.8 and CT108. Furthermore, anti-Ly-6A/E-induced IL-2 production was restored for ζ-transfected MA5.8. Thus, although induction of IL-2 by anti-Ly-6A/E depends on ζ expression, inhibition of IL-2 by anti-Ly-6A/E occurs by a ζ-independent mechanism. Interestingly, anti-Ly-6A/E, but not anti-Thy-1, inhibited anti-CD3-induced IL-2 production by MA5.8 and Ly-6E.1-transfected EL4J. Therefore, inhibition of IL-2 production by anti-Ly-6A/E was not a general property of a mAb binding to a phosphatidylinositol-linked molecule, as has been suggested for induction of IL-2 production. Taken together these data suggest that the molecular mechanisms of induction and inhibition of IL-2 production by anti-Ly6A/E are separable and expression of TCR-ζ is one variable that distinguishes these two pathways.",
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T2 - Phosphatidylinositol-anchored Ly-6A/E antagonizes T cell receptor-mediated IL-2 production by a ζ-independent pathway

AU - Codias, Elaine K.

AU - Fleming, Tony J.

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AU - Ashwell, Jonathan D.

AU - Malek, Thomas

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