Responses of T cells to ligands for the T-cell receptor.

We have learned a great deal about the recognition of MHC class II:peptide complexes by concentrating on the responses of a single cloned T-cell line, called D10. From these results, we argue for a single orientation of all CD4 T-cell receptors to their MHC ligands, based on the uneven top surface of MHC molecules, the repeated isolation of cells with T-cell receptors encoded in the same V alpha and V beta genes after peptide immunization, the proposed role of CD4 in aligning the sites, and the apparently invariant orientation of the antigenic peptide in the peptide binding groove of MHC class II molecules. We also argue in favor of a model of T-cell activation that involves conformational change as well as cross linking of the T-cell receptors. Finally, we show in other systems that the structure of the peptide can determine the differentiation fate of naive CD4 T cells in vivo or in vitro.