THE ASSEMBLY AND STABILITY OF MHC CLASS II-(ALPHA-BETA)(2) SUPERDIMERS

X-ray crystallography of several MHC class II molecules revealed a str ucture described as a dimer of heterodimers, or a superdimer. This dis covery led to the hypothesis that MHC class II molecules may interact with the TCR and CD4 as an (alpha beta)(2) superdimer, potentially pro viding more stable and stimulatory interactions than can be provided b y the simple cup heterodimer alone. In this study, using chemical cros s-linking, we provide evidence for the existence of the superdimers on the surface of B cells. We further characterize the superdimers and d emonstrate that in lysates of B cells, I-E-k dimers and superdimers ar e 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 12 0-kDa superdimers, indicating that I-E-k has an intrinsic ability to f orm 120-kDa complexes in the absence of other cellular components. Pep tide mapping showed that the alpha beta and (alpha beta)(2) complexes are closely related and that the superdimers do not contain additional polypeptides not present in the dimers, The (alpha beta)(2) complex d isplays thermal and pH stability similar to that of the cup complex, b oth being denatured by SDS at temperatures above 50 degrees C and at a pH below 5, These data support the model that MHC class II has an int rinsic ability to assume the (alpha beta)(2) superdimeric conformation , which may be important for interactions with the TCR and CD4 corecep tor.