THE ROLE OF CD45 AND CD45-ASSOCIATED MOLECULES IN T-CELL ACTIVATION

CD45 (lymphocyte common antigen) is a receptor-linked protein tyrosine phosphatase that is expressed on all leucocytes, and which plays a cr ucial role in the function of these cells. On T cells the extracellula r domain of CD45 is expressed in several different isoforms. and the p articular isoform(s) expressed depends on the particular subpopulation of cell, their state of maturation, and whether or not they have prev iously been exposed to antigen. It has been established that the expre ssion of CD45 is essential for the activation of T cells via the TCR, and that different CD45 isoforms display a different ability to suppor t T cell activation. Although the tyrosine phosphatase activity of the intracellular region of CD45 has been shown to be crucial for support ing signal transduction from the TCR, the nature of the ligands for th e different isoforms of CD45 have been elusive. Moreover, the precise mechanism by which potential ligands may regulate CD45 function is unc lear. Interestingly, in T cells CD45 has been shown to associate with numerous molecules, both membrane associated and intracellular; these include components of the TCR-CD3 complex and CD4/CD8. In addition, CD 45 is reported to associate with several intracellular protein tyrosin e kinases including p56(kk) and p59(fyn) of the src family, and ZAP-70 of the Syk family, and with numerous proteins of 29-34 kDa. These CD4 5-associated molecules may play an important role in regulating CD45 t yrosine phosphatase activity and function. However, although the role of some of the CD45-associated molecules (e.g. CD45-AP and LPAP) has b ecome better understood in recent years, the role of others still rema ins obscure. This review aims to summarize recent findings on the role of CD45 and CD45-associated molecules in T cell activation, and to hi ghlight issues that seem relevant to ongoing research in this area.