Pyridoxal 5'-phosphate as a novel weapon against autoimmunity and transplant rejection

Activation of CD4 T cells by antigen-presenting cells is required for the full expression of most autoimmune diseases and allogeneic transplant rejection. The extracellular part of CD4 molecule is composed of four domains, D1-D4. CD4 binds to MHC class II via its D1 and D2 domains. Pyridoxal 5'-phosphate (PLP) binds very tightly to the D1 domain of CD4 and therefore could interfere with proper CD4-MHC II interaction. Nonincorporation of CD4 into the activation complex can result in T cell apoptosis and anergy to autoantigen (s). Occupancy of D1 by PLP may prevent the proper protein-protein interactions of the CD4 molecule itself, which are important in T cell activation. PLP may also interfere with the dimerization of CD4 molecules, which occurs during T cell activation, or with the interaction of this dimer with other molecules on the T cell surface, such as CD45, thereby further rendering T cells anergic or driven to apoptosis. Therefore, PLP may have utility in the treatment of autoimmunity and transplant rejection. Furthermore, as the interaction of the HIV gp120 and CD4 occurs via D1, PLP is supposed to have anti-HIV effect as well. PLP may prove of special utility in the treatment of patients affected with both autoimmunity and HIV, for whom the routine immunosuppressives are contraindicated.