Immunodominance of cytotoxic T lymphocyte epitopes co‐injected in vivo and modulation by interleukin‐12

AbstractImmunodominance (ID) of T cell epitopes is a well‐documented phenomenon that might have profound significance in the evolution of T cell responses to pathogens, tumors, autoantigens and vaccines. With the intention of developing vaccines composed of several cytotoxic T cell (CTL) epitopes, we injected mice with peptide mixtures containing two to five CTL epitopes and observed clear patterns of ID. In a first case, ID strictly correlated with the competitor activity of the individual peptides for H‐2Kd, whereas in a second case, the absence of correlation between ID and competitor activity, binding affinity, half‐life of the peptides in serum, induction of proliferation in vitro and the individual immunogenicity of the peptides, suggested to us that ID of co‐injected CTL epitopes can be determined both at the peptide level (binding affinity to H‐2Kd) and at the T cell level. This hypothesis is supported by our finding that interleukin‐12 strongly modulates ID when it is not correlated with MHC binding.