International Immunology Advance Access originally published online on March 21, 2007
International Immunology 2007 19(4):497-507; doi:10.1093/intimm/dxm016
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Avidity of CD8 T cells sharpens immunodominance
1 Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1578, USA
2 Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Correspondence to: I. M. Belyakov; E-mail: igorbelyakov{at}yahoo.com; and to J. A. Berzofsky; Email: berzofsk{at}helix.nih.gov
In the course of viral infection, the immune system exploits only a fraction of the available CTL repertoire and focuses on a few of a myriad of potentially antigenic peptides. This phenomenon, known as immunodominance, depends on a number of factors, including antigen processing and transport, MHC binding, competition for antigen-presenting cells, availability of the CD8 T cell repertoire and other mechanisms that function largely by restricting the immune response. Here we elucidate a novel mechanism that increases the immunodominance of the epitope rather by enhancing the immune response. Using a peptide-specific MHC-restricted mAb and functional assays of CTL activation, we show that T cells with high avidity for the immunodominant, H-2Dd restricted, P18-I10 epitope expand rapidly following immunization, and this expansion in turn determines the level of the P18-I10 epitope immunodominance. This proliferation has little dependence on the number of MHC–peptide complexes. Since most self-reactive T cells of high avidity are depleted in the thymus, the selection of immunodominant epitopes based on the expansion of high-avidity T cells in the periphery reduces the potential for autoimmunity.
Keywords: Immunodominance, cytotoxic, T lymphocytes, avidity, epitope
Transmitting editor: T. Sasazuki
Received 20 September 2006, accepted 24 January 2007.