Consequences of inter cellular molecular transfer in vitro and in vivo

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Cell to cell interaction within the immune system takes place within the immunological synapse. As a consequence, surface molecules can be exchanged. We will use an antibody-directed toxin approach to deplete recipient cells that have acquired donor MHC class II molecules (and vice versa) to study their contribution towards the rejection process in a mouse kidney allograft model. An anti donor MHC class II antibody will be used to direct a 'toxin' (gelonin) towards cells that express donor class II MHC molecules. If the donor (but not recipient) cells are resistant to the toxin, then only recipient (Multi drug resistant gene knockout mice which are toxin sensitive) cells that have acquired donor class II MHC molecules will be lysed. This will enable us to determine the relative contribution of this process to the alloresponse. We have synthesized this immunotoxin and demonstrated its effectiveness both in vitro and in vivo. In vitro experiments will also be performed to investigate the ability of the phenomenon to link the direct and indirect antigen presentation pathways. Understanding the consequences of MHC transfer will also have important implications in other fields where antigen presentation is involved, such as tumor immunology, vaccination, infection and auto-immune diseases.