Transmembrane domain sequences regulate the association of MHC- class II with lipid raft microdomains (106.19)

Abstract

Abstract MHC II is known to be present in cholesterol-dependent lipid raft plasma membrane microdomains, and this association is important for MHC II- dependent activation of CD4 T cells by Dendritic cells (DCs). Until now it is not clear what regulates MHC II lipid raft association. In the present study we attempt to define the signals present in the MHC II transmembrane (TM) domain that regulate MHC II association with lipid rafts. Palmitoylation of cysteine residues is a well-known modification that often results in lipid raft association of TM protein and each MHC II I-Ab subunit contains a TM cysteine. We therefore expressed MHC II-α and β-chains containing TM domain cysteine → serine mutants in DCs obtained from MHC II null mice and analyzed MHC II lipid raft association. These experiments showed that the mutation of the TM cysteine residues actually enhanced MHC II raft localization about 3 fold. We also examined the role of the entire MHC II TM domain in lipid raft association. Replacement of the MHC II-α and β-chain TM domains with that of the non-raft protein ICAM 1 reduces MHC II lipid raft association 5 fold. We are currently examining the role of TM domain sequences present in each MHC II subunit in an attempt to identify dominant raft localization sequences in MHC II.