The Ia.2 Epitope Defines a Subset of Lipid Raft-Resident MHC Class II Molecules Crucial to Effective Antigen Presentation
Busman-Sahay, Kathleen, Sargent, Elizabeth, Harton, Jonathan A. and Drake, James R. (2011) The Ia.2 Epitope Defines a Subset of Lipid Raft-Resident MHC Class II Molecules Crucial to Effective Antigen Presentation. The Journal of Immunology, 186, (12), 6710-6717. (doi:10.4049/jimmunol.1100336).
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Previous work established that binding of the 11-5.2 anti–I-Ak mAb, which recognizes the Ia.2 epitope on I-Ak class II molecules, elicits MHC class II signaling, whereas binding of two other anti–I-Ak 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-Ak molecules predominantly found within membrane lipid rafts. Functional studies demonstrate that the Ia.2-bearing subset of I-Ak 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-Ak class II molecules possessing a b-chain–tethered hen egg lysosome peptide lack the Ia.2 epitope and fail to partition into lipid rafts. Moreover, cells expressing Ia.22 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.
|Subjects:||Q Science > QD Chemistry
Q Science > QH Natural history > QH301 Biology
|Divisions:||University Structure - Pre August 2011 > School of Ocean & Earth Science (SOC/SOES)
Faculty of Natural and Environmental Sciences > Ocean and Earth Science > Ocean Biochemistry & Ecosystems
|Date Deposited:||10 Jun 2011 12:29|
|Last Modified:||11 Jan 2012 13:22|
|Contributors:||Busman-Sahay, Kathleen (Author)
Sargent, Elizabeth (Author)
Harton, Jonathan A. (Author)
Drake, James R. (Author)
|Date:||15 June 2011|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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