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 language | English |
|---|---|
| Pages (from-to) | 1825-1832 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 149 |
| Issue number | 6 |
| State | Published - Sep 15 1992 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Role of Ly-6A/E and T cell receptor-ζ for IL-2 production
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.
AU - Zacharchuk, Charles M.
AU - Ashwell, Jonathan D.
AU - Malek, Thomas
PY - 1992/9/15
Y1 - 1992/9/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0026709411&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026709411&partnerID=8YFLogxK
M3 - Article
C2 - 1387661
AN - SCOPUS:0026709411
VL - 149
SP - 1825
EP - 1832
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -