| First Author | Busman-Sahay K | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 12 | Pages | 6710-7 |
| PubMed ID | 21543648 | Mgi Jnum | J:175501 |
| Mgi Id | MGI:5285810 | Doi | 10.4049/jimmunol.1100336 |
| Citation | Busman-Sahay K, et al. (2011) The Ia.2 epitope defines a subset of lipid raft-resident MHC class II molecules crucial to effective antigen presentation. J Immunol 186(12):6710-7 |
| abstractText | 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 beta-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. |
