Functional consequences of CD4-TCR/CD3 interactions

The relative positions of CD4 and of the T cell receptor complex for antigen (TCR/CD3) determine whether signalling through the antigen receptor results in T cell growth. The following discussion focusses on those central observations which demonstrate that CD4 and the associated protein tyrosine kinase p56lck provide critical signals modulating the biological responses induced through the TCR/CD3 complex. Based on the available evidence, we suggest that antigen-mediated co-aggregation of CD4/Lck and TCR/CD3 is an obligate activation signal and that, in its absence, signalling through TCR alpha beta induces T cell death. The role of CD4 in self-non-self discrimination would therefore be critical and would provide a mechanism for the maintenance of peripheral T cell tolerance to non-major histocompatibility complex-related self-antigens.