Triggering of CD8+ cytotoxic T lymphocytes via CD3-epsilon differs from triggering via alpha/beta T cell receptor. CD3-epsilon-induced cytotoxicity occurs in the absence of protein kinase C and does not result in exocytosis of serine esterases.
The requirement for protein kinase C (PKC) during triggering of murine CD8+ CTL was investigated. To this, CTL were depleted for PKC by pretreatment with PMA. This procedure neither influenced alpha/beta-TCR, CD3-epsilon, CD8, CD2, and lymphocyte function-associated Ag-1 expression, nor CTL-target cell conjugate formation. Although cytolytic effector function of PKC-depleted CTL triggered via alpha/beta-TCR structures was completely inhibited, target cell lysis induced via CD3-epsilon remained unaffected. Furthermore this PKC-independent cytolysis pathway was not associated with the release of serine esterases. Analyses at the clonal level revealed that PKC depletion blocked the cytolytic response of up to 95% of alpha/beta-TCR triggered CTL clones. The data suggest the existence of a distinct signaling pathway triggered via CD3-epsilon that is not associated with exocytosis of serine esterases and probably independent of PKC.
Hengel
H
H
Department of Medical Microbiology and Immunology, University of Ulm Albert-Einstein-Allee 11, Germany.
Wagner
H
H
Heeg
K
K
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis* / Q000502:physiology*; D017252:CD3 Complex; D016827:CD8 Antigens; D002118:Calcium / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D004950:Esterases / Q000378:metabolism*; D005089:Exocytosis; D051379:Mice; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011493:Protein Kinase C; D004950:Esterases; C022635:serine esterase; D002118:Calcium