The response of T cells to antigen involves the participation of a number of distinct receptor-ligand engagements. The major players in the recognition of complexes of major histocompatibility complex molecules and peptide antigens are the T-cell receptors and the co-receptors CD4 and CD8. Progress in understanding the physical structures of these molecules, and how complexes between them are formed, is helping our understanding of how they participate in regulating the signals transduced to T cells.