Peptide modification or blocking of CD8, resulting in weak TCR signaling, can activate CTL for Fas- but not perforin-dependent cytotoxicity or cytokine production.

Kessler, B; Hudrisier, D; Schroeter, M; Tschopp, J; Cerottini, J; Luescher, I

Journal article

Peptide modification or blocking of CD8, resulting in weak TCR signaling, can activate CTL for Fas- but not perforin-dependent cytotoxicity or cytokine production.

Abstract:: This study describes a form of partial agonism for a CD8+ CTL clone, S15, in which perforin-dependent killing and IFN-gamma production were lost but Fas (APO1 or CD95)-dependent cytotoxicity preserved. Cloned S15 CTL are H-2Kd restricted and specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS 252-260 (SYIPSAEKI). The presence of a photoactivatable group in the epitope permitted assessment of TCR-ligand binding by TCR photoaffinity labeling. Selective activation of Fas-dependent killing was observed for a peptide-derivative variant containing a modified photoreactive group. A similar functional response was obtained after binding of the wild-type peptide derivative upon blocking of CD8 participation in TCR-ligand binding. The epitope modification or blocking of CD8 resulted in an > or = 8-fold decrease in TCR-ligand binding. In both cases, phosphorylation of zeta-chain and ZAP-70, as well as calcium mobilization were reduced close to background levels, indicating that activation of Fas-dependent cytotoxicity required weaker TCR signaling than activation of perforin-dependent killing or IFN-gamma production. Consistent with this, we observed that depletion of the protein tyrosine kinase p56(lck) by preincubation of S15 CTL with herbimycin A severely impaired perforin- but not Fas-dependent cytotoxicity. Together with the observation that S15 CTL constitutively express Fas ligand, these results indicate that TCR signaling too weak to elicit perforin-dependent cytotoxicity or cytokine production can induce Fas-dependent cytotoxicity, possibly by translocation of preformed Fas ligand to the cell surface.

Publication status:: Published

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Kessler, B., Hudrisier, D., Schroeter, M., Tschopp, J., Cerottini, J., & Luescher, I. (1998). Peptide modification or blocking of CD8, resulting in weak TCR signaling, can activate CTL for Fas- but not perforin-dependent cytotoxicity or cytokine production. Journal of Immunology, 161(12), 6939–6946.

MLA Style

Kessler, B, et al. “Peptide Modification or Blocking of CD8, Resulting in Weak TCR Signaling, Can Activate CTL for Fas- but Not Perforin-Dependent Cytotoxicity or Cytokine Production.” Journal of Immunology, vol. 161, no. 12, 1998, pp. 6939–46.

Chicago Style

Kessler, B, D Hudrisier, M Schroeter, J Tschopp, J Cerottini, and I Luescher. 1998. “Peptide Modification or Blocking of CD8, Resulting in Weak TCR Signaling, Can Activate CTL for Fas- but Not Perforin-Dependent Cytotoxicity or Cytokine Production.” Journal of Immunology 161 (12): 6939–46.
Print