An essential step in the presentation of antigenic peptide by MHC class I molecules to cytolytic T cells is the binding of a relevant peptide. These peptides are produced by the proteolysis of cytosolic proteins and a sample of the resulting peptides are pumped from the cytosol into the endoplasmic reticulum in a process involving the TAP molecules. Here they can bind to nascent major histocompatibility complex (MHC) class I molecules which then complete their folding pathway and exit to the cell surface where the process of recognition by T cells takes place. MHC molecules are thus peptide receptors that bind peptides with both specificity and promiscuity. The peptides bound by a. specific MHC class I molecule tend to conform to an allele-specific motif; a pattern of residues that is conserved or nearly conserved at specific positions along the polypeptide backbone. This collection of specific residues, termed anchors (Falk et al. 1991), forms the MHC binding agretope (the minimal requirement for stable binding to the MHC molecule). The wide variety of T-cell epitopes is largely generated at positions that are variable, where no conservation is observed in the residue type amongst the peptides binding to a given MHC molecule. The amino acid residues at these positions, together with the upward facing residues of the MHC molecule, form the variable surface used by the T-cell receptor to distinguish between self and non-self_ c. J. Thorpel (~)• DS Moss-E J. Travers Laboratory of Molecular Biology and Bloomsbury Molecular Recognition Centre, Department of Crystallography, Birkbeck College, Malet Street, London WC1E 7HX, England