16: Diffusion of Individual MHC Molecules in Membranes
A question that always arose in discussion of T cell – target cell recognition was the possible subtle aggregation of molecules on the target cell surface, before cell-cell contact. One of my graduate students, Marja Vrljic combined efforts with Stephanie Nishimura to measure the rate of lateral diffusion of individual MHC molecules transfected into CHO cells. (Stephanie was a graduate of W.E. Moerner.) In one case the MHC molecule was a full length transmembrane protein, and in the other case the molecule was GPI linked to the membrane, both cases representing typical modes of attachment of membrane proteins to the bilayer. The motion of these molecules in the cell membranes was found to be Brownian with no evidence of the molecules associating with one another, The derived diffusion coefficients were only an order of magnitude less than those reported for lipids in bilayers by Devaux (see above). The elegance in this experiment is related to the fact that the fluorescent probe was attached to an antigenic peptide bound in turn to the MHC molecule, and the combination was fully functional in antigen presentation to T helper cells (463). Later work showed that cholesterol in the membranes was essential for the mobility of the MHC molecules (469).