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The Assembly and Stability of MHC Class II-(ß)₂ Superdimers¹

Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208

X-ray crystallography of several MHC class II molecules revealed a structure described as a dimer of heterodimers, or a superdimer. This discovery led to the hypothesis that MHC class II molecules may interact with the TCR and CD4 as an (ß)₂ superdimer, potentially providing more stable and stimulatory interactions than can be provided by the simple ß heterodimer alone. In this study, using chemical cross-linking, we provide evidence for the existence of the superdimers on the surface of B cells. We further characterize the superdimers and demonstrate that in lysates of B cells, I-E^k dimers and superdimers are derived from the same population of I-E^k molecules. Purified, I-E^k molecules in solution also exist as a mixture of 60-kDa dimers and 120-kDa superdimers, indicating that I-E^k has an intrinsic ability to form 120-kDa complexes in the absence of other cellular components. Peptide mapping showed that the ß and (ß)₂ complexes are closely related and that the superdimers do not contain additional polypeptides not present in the dimers. The (ß)₂ complex displays thermal and pH stability similar to that of the ß complex, both being denatured by SDS at temperatures above 50°C and at a pH below 5. These data support the model that MHC class II has an intrinsic ability to assume the (ß)₂ superdimeric conformation, which may be important for interactions with the TCR and CD4 coreceptor.

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