title: The Ia.2 epitope defines a subset of lipid raft-resident MHC class II molecules crucial to effective antigen presentation.
abstract: Previous work established that binding of the 11-5.2 anti-I-A(k) mAb, which recognizes the Ia.2 epitope on I-A(k) class II molecules, elicits MHC class II signaling, whereas binding of two other anti-I-A(k) mAbs that recognize the Ia.17 epitope fail to elicit signaling. Using a biochemical approach, we establish that the Ia.2 epitope recognized by the widely used 11-5.2 mAb defines a subset of cell surface I-A(k) molecules predominantly found within membrane lipid rafts. Functional studies demonstrate that the Ia.2-bearing subset of I-A(k) class II molecules is critically necessary for effective B cell-T cell interactions, especially at low Ag doses, a finding consistent with published studies on the role of raft-resident class II molecules in CD4 T cell activation. Interestingly, B cells expressing recombinant I-A(k) class II molecules possessing a β-chain-tethered hen egg lysosome peptide lack the Ia.2 epitope and fail to partition into lipid rafts. Moreover, cells expressing Ia.2(-) tethered peptide-class II molecules are severely impaired in their ability to present both tethered peptide or peptide derived from exogenous Ag to CD4 T cells. These results establish the Ia.2 epitope as defining a lipid raft-resident MHC class II conformer vital to the initiation of MHC class II-restricted B cell-T cell interactions.
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Busman-Sahay
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sargent
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Harton
authors.forename: James R
authors.initials: JR
authors.lastname: Drake
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000939:Epitopes; D000949:Histocompatibility Antigens Class II