Author(s): VemulaVani1*,Sanjay Prasad2and Muthukumaran Sivanandham
Interaction of CD40 ligand (CD40L) with CD40 receptor is one of the most immunologically important interactions that involve in the regulation of T cell dependent B cell proliferation, differentiation and antibody production. Mutation in CD40L is associated with several diseases. Therefore, interfering CD40L interaction with CD40 may have important therapeutic applications. Using the three dimensional structure of CD40-CD40L complex, three small CD40L mimetic molecules have been designed using computational techniques. Out of these three molecules, two molecules viz. ammonium benzoyltrimethyl chloride and N-benzhydrylbenzamide were synthesized and characterized. The third molecule, 3-( Dimethylamino) propiophenone hydrochloride was purchased from a chemical supplier. These three mimetic molecules were tested for their potential to activate B cell proliferation and immunoglobulin isotype switching in the presence of Mycobacterial antigen, PPD. It was found that these molecules at their optimal concentrations have shown to proliferate B cells through the help provided by activated T cells. Moreover, these molecules have switched the IgM isotype to IgG isotype antibody to PPD. Hence, these three molecules can be considered as ideal candidates for further development of novel immunotherapeutic agents.