Immunological activity of covalently linked T-cell epitopes

Immune response to proteins necessarily involve the recognition by T lymphocytes of a peptide or peptides derived from a a protein complexed with a major histocompatibility antigen. Th T-cell response of BALB/c mice to the bacteriophage lambda cI repressor protein (residues 1-102) is directed predominantly towards the epitope contained within a single peptide encompassing residues 12-26 (refs 1, 2). Similar phenomenon of immunodominance of a particular peptide have also been observed in other protein systems. The mechanism that have been suggested to account for the focusing of the T-cell response are partial deletion in the T cell repertoire, biased antigen processing, and competition for binding to the presenting molecule, the major histocompatibility complex encoded class II transplantation antigen. In a model system with a polypeptide containing two synthetically linked immunologically active epitopes, we now demonstrate the existence of a hierarchy between these epitopes, so that the immune response elicited is directed mainly towards the more immunogenic epitope whereas the less immunogenic epitope elicits little or no T cell reactivity. in addition the same hierarchy of dominance is also apparent when the polypeptide id used to induce tolerance in the periphery in adult mice.