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Immunological activity of covalently linked T-cell epitopes


IMMUNE responses to proteins necessarily involve the recognition by T lymphocytes of a peptide or peptides derived from a protein complexed with a major histocompatibility antigen. The T-cell response of BALB/c mice to the bacteriophage Λ cI represser protein (residues 1-102) is directed predominantly towards the epitope contained within a single peptide encompassing residues 12–26 (refs 1, 2). Similar phenomena of immunodominance of a particular peptide have also been observed in other protein systems3–6. The mechanisms that have been suggested to account for the focusing of the T-cell response7are 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 is used to induce tolerance in the periphery in adult mice. The chimaeric peptide can induce tolerance only towards the more immunogenic epitope. These experiments indicate that the rules governing antigen processing and presentation that result in T-cell activation are apparently the same as the rules that govern the processes resulting in the induction of tolerance.

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Ria, F., Chan, B., Scherer, M. et al. Immunological activity of covalently linked T-cell epitopes. Nature 343, 381–383 (1990).

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