T and B cell receptors discriminate major histocompatibility complex class II conformations influenced by the invariant chain

Direct recognition of major histocompatibility complex (MHC) molecules may occur when T cells are positively selected in the thymus and also during recognition of non-self MHC molecules. Since peptide recognition and binding of particular monoclonal antibodies is strongly influenced by the invariant chain (Ii) of the class II molecule, we have asked whether Ii also affects recognition of non-self MHC molecules by T cells. We find that Ii binding alters MHC class II conformation as detected by a monoclonal antibody, and that this alteration is retained in cell surface MHC class II molecules after Ii dissociates. This altered conformation also affects recognition by allogeneic T cells. Normal T cells and T cell clones preferentially recognize MHC class II molecules that have been associated with Ii, suggesting that thymic selection may be influenced by MHC conformation independently of specific peptide binding.