The structure of MHC class II: a role for dimer of dimers

Abstract The MHC class II molecules, expressed by antigen presenting cells, are heterodimers composed of an α and a β chain, which function to present processed antigen to helper T cells. The human MHC class II molecules, HLA-DR1 and HLA-DR3, crystallized not as monomers, but rather dimers of αβ heterodimers. The ‘dimer of dimers’ or ‘superdimer’ structure led to speculation that the binding of T-cell receptors to monomeric class II molecules on the antigen presenting cell surface may affect dimerization and thus initiate signaling both in the T cell and in the antigen presenting cell. Recent biochemical analyses of the mouse MHC class II E k molecule provide evidence that dimers of class II heterodimers form in the absence of T cells. Although such dimers were shown to augment T-cell stimulation, the dimerization of class II molecules alone is unlikely to initiate signal transduction. However, dimers may be important in stabilizing weak T-cell receptor/CD4/class II interactions, allowing further multimerization of such complexes, leading to signaling.