Role of CD5 on T cells

As indicated above, CD5 is found on thymocytes and the majority of peripheral T cells. Increased expression of CD5 by a number of protein kinase C activators has suggested that this molecule is important in the activation process of T cells (and probably B1 cells). CD5 is associated with the TCR £ chain and the cytoplasmic domain of CD5 is phos-phorylated on tyrosines on activation via the TCR. This is thought to bind SH2 domain-containing proteins. Studies on peripheral T cell activation in vitro have shown a costimulatory role for CD5 on TCR-mediated proliferative responses. Thus, cross-linking of CD5 on T cells by monoclonal antibodies results in a rise in intracellular Ca2+ derived from an extracellular source (via Ca2" channels) and generation of cyclic GMP. Furthermore, solid-phase immobilization of CD5 antibodies alone provides a stimulus for interleukin 2 (IL-2) receptor induction and responsiveness to IL-2. It is thought that, along with other costimulatory interactions of molecules on T and B cells, CD5 on T cells binds to CD72 on B cells which enhances T cell and B cell activation. In contrast, in CD5 knockout mice, unlike peripheral T cells, thymocytes are hyper-responsive to stimulation through the TCR. In addition, selection of T cells expressing transgenic TCRs were abnormal in these mice indicating that CD5 plays a role as a negative regulator of TCR mediated activation during T cell development.

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