Once at the plasma membrane, peptide-loaded MHC-II (pMHC-II) complexes are displayed for recognition by CD4 T cells. T cells are exquisitely sensitive and are capable of recognizing very small amounts of pMHC-II. We first reported that pMHC-II is constitutively associated with plasma membrane microdomains, termed lipid rafts, and that raft association increases the local density of pMHC-II to support T cell activation by small numbers of pMHC-II complexes. We have also been exploring the association of MHC-II with a family of proteins termed tetraspanins, and curiously MHC-II bound to tetraspanins also appears clustered in microdomains. We are currently using genetically-engineered mice lacking specific tetraspanin proteins to investigate the extent to which tetraspanin-binding influences MHC-II microdomain association and are examining the importance of tetraspanins in antigen presenting cell function.

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National Cancer Institute (NCI)
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National Cancer Institute Division of Basic Sciences
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Bandola-Simon, Joanna; Roche, Paul A (2018) Dysfunction of antigen processing and presentation by dendritic cells in cancer. Mol Immunol :
Lei, Lei; Bandola-Simon, Joanna; Roche, Paul A (2018) Ubiquitin-conjugating enzyme E2 D1 (Ube2D1) mediates lysine-independent ubiquitination of the E3 ubiquitin ligase March-I. J Biol Chem 293:3904-3912
Kaul, Sunil; Mittal, Sharad K; Roche, Paul A (2018) A major isoform of the E3 ubiquitin ligase March-I in antigen-presenting cells has regulatory sequences within its gene. J Biol Chem 293:4478-4485
Klein, Ofir; Roded, Amit; Zur, Neta et al. (2017) Rab5 is critical for SNAP23 regulated granule-granule fusion during compound exocytosis. Sci Rep 7:15315
Cresswell, Peter; Roche, Paul A (2017) Editorial Overview: Antigen Processing and Presentation; many fingers in many pies. Curr Opin Immunol 46:v-vii
Da, Q; Shaw, T; Pradhan, S et al. (2017) Disruption of protein complexes containing protein phosphatase 2B and Munc18c reduces the secretion of von Willebrand factor from endothelial cells. J Thromb Haemost 15:1032-1039
Roche, Paul A; Cresswell, Peter (2016) Antigen Processing and Presentation Mechanisms in Myeloid Cells. Microbiol Spectr 4:
Anderson, Howard A; Roche, Paul A (2015) MHC class II association with lipid rafts on the antigen presenting cell surface. Biochim Biophys Acta 1853:775-80
Roche, Paul A; Furuta, Kazuyuki (2015) The ins and outs of MHC class II-mediated antigen processing and presentation. Nat Rev Immunol 15:203-16
Bosch, Berta; Heipertz, Erica L; Drake, James R et al. (2013) Major histocompatibility complex (MHC) class II-peptide complexes arrive at the plasma membrane in cholesterol-rich microclusters. J Biol Chem 288:13236-42

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