SIGNALING INITIATED WITH CD4-TCR OR TCR-TCR INTERACTIONS - COMPARISONOF TYROSINE PHOSPHORYLATION PATTERNS AND CD45 EFFECTS

Antigen-triggered response in T cells is mediated by the T cell recept or (TCR)/CD3-complex. This signalling, however, is modulated by a numb er of other surface molecules. Among the most important of these is th e CD4/CD8 molecule which associates with the TCR/CD3-complex and binds to the MHC complex. The molecular mechanisms involved in interactions between TCR-TCR and TCR-CD4 are not fully understood. We have earlier described an experimental model that allows us to dissect signals inv olving CD4-TCR interactions and those involving TCR-TCR interactions u sing a mouse CD4(-)CD8(-) T cell hybridoma cell-line transfected eithe r with the TCR from a mouse T-helper(2) cell-line (D10) alone or with both the TCR and the CD4 molecule. To further characterize these two d ifferent modes of signalling in T lymphocytes we have studied the tyro sine phosphorylation patterns resulting from these interactions. In ad dition, we have studied the modulatory effect of the CD45 molecule on these interactions. In contrast to some earlier reports, we found that both the patterns of induced tyrosine phosphorylation and the effects of CD45 modulation were essentially similar in the CD4-TCR and the TC R-TCR signal transduction cascades. The results are consistent with a purely synergistically amplifying function for CD4 on the TCR-mediated signalling. (C) 1998 Elsevier Science B.V. All rights reserved.