Ia molecules are heterogeneous in several respects including post-translational processing and variable association with invariant chain (I?i?) and a specific chondroitin sulfate proteoglycan (CSPG) which hss only recently been discovered. In this work, the subcellular localization of the variously modified forms of Ia molecules will be determined, with particular attention focussed on the possibility that specialized areas of the cell membrane such cytoskeletally associated regions or coated pits may segregate a subset of Ia molecules specialized in post-translational modifications and/or in association with I?i? or CSPG. Recovery of specialized areas of plasma membrane will employ membrane fractionation techniques, isolation of coated vesicles, differential detergent susceptibility and vectorial labeling. The possibility that post-translational modificaton or I?i?/CSPG association of Ia governs an internal housekeeping functon such as targeting to particular subcellular sites will be evaluated using kinetic labeling techniques together with cell fractionation. The possibility thst Ia molecules which recycle from the surface to an intracellular location have different forms in the two locations will be assessed. The rate of cycling will be compared to that of a known receptor in activated and resting lymphocytes to determine whether the rate is like that of a receptor, and whether the rate can be modulated. (AG)
