Signal transduction through the T cell receptor-CD3 complex: evidence for heterogeneity in receptor coupling

Virtually all cells require some sort of communication between the outside of the cell and the inside. External events, often the binding of a molecule to a specific receptor on a cell surface, signal the initiation of a complex series of events within the cell. Nowhere is this signalling more evident than in the immune system. In the case of T cells, the cell responds to the presentation of specific antigen with a series of changes collectively called 'activation'. The activation of a T cell apparently begins when the T cell receptor is presented with specific antigen. The T cell receptor is associated with a second molecular complex, called CD3, which is thought to transduce the signal, that is, convert it into biochemical changes within the cell. The nature of such transduction is a major problem for modern biology. Now, however, it has been found that the same molecular complex, the T cell receptor/CD3 complex, or TCR-CD3, may in fact accomplish this transduction differently in different cells. Two different cell lines were used to examine the molecular events following TCR-CD3 stimulation. Both the HPB-ALL cell line and the Jurkat cell line express large quantities of TCR-CD3 on their cell surfaces. However, the Jurkat cell line responds to stimulation with a mobilization of intracellular calcium and the production of inositol phosphate. (Inositol phosphate is another so-called 'second messenger', which is used by many cells to signal the occurrence of specific biochemical events.) When the same stimulation of HPB-ALL is examined, no production of inositol phosphate is observed. Both cells were found to have normal levels of the enzyme calcium-induced phospholipase C, a key enzyme in the transduction process. Therefore, the absence of inositol phosphate production cannot be attributed to the absence or relative lack of this enzyme. In the HPB-ALL cell line, the events occurring on the cell surface are uncoupled from the activation of this enzyme. Similarly, the activity of the enzyme protein kinase C, which signals by adding a phosphate group to proteins, was also uncoupled from the stimulation of the TCR-CD3 complex in the HPB-ALL cells. The results indicate that the same cell surface receptor may operate by stimulating different intracellular events in different cell lines. (Consumer Summary produced by Reliance Medical Information, Inc.)