CD8 T cells mediate antiviral immunity but are also implicated in autoimmunity.1,–,2 Responses elicited by immunogenic peptides target only a minute fraction of all potential peptide determinants, a phenomenon termed immunodominance.3–4 Immunodominance can be readily assessed for CD8 T-cell responses targeting Epstein–Barr virus (EBV), a herpes family virus that establishes life-long persistent infection in over 90% of the adult population.5 Here we hypothesised that, largely independent of an individual's medical condition, immunosuppression is inefficient at shifting established immunodominance. To test this hypothesis, we quantitatively assessed CD8 T-cell responses targeting defined EBV-derived peptides in individuals with differing medical histories exposed to immunosuppressive regimens of variable intensity.

The frequency of interferon γ-secreting T cells specific for any of 91 defined EBV-derived major histocompatibility complex I epitopes, optimally restricted by a wide range of human leucocyte antigen class I alleles, was quantified by enzyme-linked immunospot assays (ELISpot).6 In …