MHC CLASS-II MOLECULES THAT LACK CYTOPLASMIC DOMAINS ARE ASSOCIATED WITH THE CYTOSKELETON

MHC class II molecules, composed of alpha- and beta-chain heterodimers , are required for Ag presentation. The carboxyl-terminal domains of c lass II molecules are believed to mediate the location of class II in the plasma membrane and are important for signal transduction and Ag p resentation. These domains contain typical transmembrane sequences, an d cytoplasmic sequences of 12 or 18 amino acids for the alpha- and bet a-chains, respectively. We examined these domains to determine whether they linked class II molecules to the actin-based cytoskeleton. Our a nalyses of class Il-cytoskeleton interactions, such as a colocalizatio n with actin filaments during capping, association with the detergent- insoluble cytoskeleton, and direct binding of filamentous actin, revea led that both the cytoplasmic and transmembrane domains contributed to class II interactions with the cytoskeleton. Detergent-extracted and immunoprecipitated full-length class II molecules had quantitatively s tronger interactions with the cytoskeleton than did molecules with del eted cytoplasmic domains. A secondary Ab, which was used to cross-link primary Ab bound to class II, up-regulated the class Il-cytoskeletal associations. This association was efficiently inhibited by dihydrocyt ochalasin B, but only partially disrupted by chlorpromazine. The mecha nism of interaction with actin filaments after ligation of class II oc curred without a measurable increase in filamentous actin levels. This suggested that enhanced class Il-cytoskeleton associations involved a rearrangement of existing actin filaments, possibly through the multi ple kinases that are activated after class II transmembrane signaling.