Immunodominance of cytotoxic T lymphocyte epitopes co-injected in vivo and modulation by interleukin-12.
Immunodominance (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.
Eberl
G
G
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Kessler
B
B
Eberl
L P
LP
Brunda
M J
MJ
Valmori
D
D
Corradin
G
G
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000276:immunology; D004357:Drug Synergism; D005260:Female; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000494:pharmacology; D015497:HIV-1 / Q000276:immunology; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000187:drug effects* / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D018664:Interleukin-12 / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009975:Orthomyxoviridae / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D015699:HIV Envelope Protein gp120; D016056:Immunodominant Epitopes; D014758:Viral Core Proteins; D018664:Interleukin-12