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Volume 272, Number 27, Issue of July 4, 1997 pp. 17055-17060
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Decreased Endosomal Delivery of Major Histocompatibility Complex Class II-invariant Chain Complexes in Dynamin-deficient Cells

(Received for publication, February 26, 1997, and in revised form, April 24, 1997)

From The R. W. Johnson Pharmaceutical Research Institute, San Diego, California 92121

Major histocompatibility complex class II molecules are heterodimeric cell surface molecules which acquire antigenic peptides in the endosomal/lysosomal system. Invariant chain (Ii), a third chain which is associated with class II molecules intracellularly mediates the endosomal targeting, but it is debated whether class II molecules reach the endosomal system mainly from the trans-Golgi network or via the cell surface.

Dynamin is a cytosolic GTPase which is necessary for the formation of clathrin-coated vesicles from the plasma membrane, but which is not required for vesicle formation from the trans-Golgi network. Here we have used HeLa cells expressing a dominant negative form of dynamin to show that inhibition of clathrin-mediated uptake from the plasma membrane leads to accumulation of transfected Ii-class II complexes at the cell surface, while delivery of such complexes to endosomes/lysosomes is decreased. Our data therefore suggest that in this experimental system the majority of Ii-class II complexes traverse the cell surface before they reach the endosomal system.

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