CD4-independent signal transduction through the T-cell receptor (TCR/CD3).
The membrane-bound CD4 glycoprotein has been proposed to act like a co-receptor along with the T-cell antigen receptor (TCR/CD3) during ligand recognition and cell activation. Due to its association with the protein tyrosine kinase (PTK) p56lck, CD4 is believed to transduce a signal and support CD3 activation of T cells. In this study we have shown that CD3 ligation on murine T-cell hybridomas induces tyrosine phosphorylation of proteins, including phospholipase C-gamma 1 (PLC gamma 1), both in the presence as well as in the absence of CD4-linked p56lck. Furthermore, using HPB clones deficient in CD3/PTK association, it has been found that the presence of CD4/p56lck does not overcome the defect in signalling. Not even co-aggregation of CD4 with CD3 triggers tyrosine phosphorylation of proteins in these cells. Together, the present results indicate that CD3-linked PTK(s) plays a primary role in the induction of signalling through TCR/CD3, and the presence of CD4/p56lck is neither necessary nor sufficient to elicit these events. In the light of these results a possible role for CD4 in antigen presentation has been proposed.
Department of Pathology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, Massachusetts.
C B
CB
Granja
C S
CS
Gozashti
J D
JD
Dasgupta
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D006825:Hybridomas; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D017252:CD3 Complex; D015704:CD4 Antigens; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)