title: Antigen-B Cell Receptor Complexes Associate with Intracellular major histocompatibility complex (MHC) Class II Molecules.
abstract: Antigen processing and MHC class II-restricted antigen presentation by antigen-presenting cells such as dendritic cells and B cells allows the activation of naïve CD4+ T cells and cognate interactions between B cells and effector CD4+ T cells, respectively. B cells are unique among class II-restricted antigen-presenting cells in that they have a clonally restricted antigen-specific receptor, the B cell receptor (BCR), which allows the cell to recognize and respond to trace amounts of foreign antigen present in a sea of self-antigens. Moreover, engagement of peptide-class II complexes formed via BCR-mediated processing of cognate antigen has been shown to result in a unique pattern of B cell activation. Using a combined biochemical and imaging/FRET approach, we establish that internalized antigen-BCR complexes associate with intracellular class II molecules. We demonstrate that the M1-paired MHC class II conformer, shown previously to be critical for CD4 T cell activation, is incorporated selectively into these complexes and loaded selectively with peptide derived from BCR-internalized cognate antigen. These results demonstrate that, in B cells, internalized antigen-BCR complexes associate with intracellular MHC class II molecules, potentially defining a site of class II peptide acquisition, and reveal a selective role for the M1-paired class II conformer in the presentation of cognate antigen. These findings provide key insights into the molecular mechanisms used by B cells to control the source of peptides charged onto class II molecules, allowing the immune system to mount an antibody response focused on BCR-reactive cognate antigen.
authors.affiliation: Center for Cardiovascular Sciences, Albany Medical College, Albany, New York 12208.
authors.forename: Margarida
authors.initials: M
authors.lastname: Barroso
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208.
authors.forename: Heidi
authors.initials: H
authors.lastname: Tucker
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208.
authors.forename: Lisa
authors.initials: L
authors.lastname: Drake
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Nichol
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208. Electronic address: drakej@mail.amc.edu.
authors.forename: James R
authors.initials: JR
authors.lastname: Drake
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D031541:Fluorescence Resonance Energy Transfer; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D000949:Histocompatibility Antigens Class II; D046912:Multiprotein Complexes; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins
keywords: B cell receptor (BCR); FRET; MHC; antigen presentation; antigen processing; antigen-presenting cell (APC); imaging; lymphocyte