Asynchronous differentiation of CD8 T cells that recognize dominant and cryptic antigens

J Immunol. 2006 Dec 15;177(12):8466-75. doi: 10.4049/jimmunol.177.12.8466.

Abstract

Restriction of T cell responses to a few epitopes (immunodominance) is a central feature of immune responses. We analyzed the entire transcriptome of effector CD8 T cells specific for a dominant (H7(a)) and a cryptic (HY) mouse Ag and performed a longitudinal analysis of selected T cell differentiation markers. We found that Ag specificity had a relatively modest influence on the repertoire of genes that are transcriptionally modulated by the CD8 T cell differentiation program. Although the differentiation programs of anti-H7(a) and anti-HY T cells were similar, they did not progress simultaneously. The expansion peak of anti-H7(a) T cells was reached on day 10 while that of anti-HY T cells was attained on days 15-20. Between days 10 and 20, anti-H7(a) T cells were in the contraction phase and anti-HY T cells in the expansion phase. Furthermore, expansion and development of effector function were well-synchronized in anti-H7(a) T cells but were disconnected in anti-HY T cells. We propose that, by leading to selective expansion of the fittest CD8 T cells, immunodominance may be beneficial to the host. Inhibition of the T cell response to cryptic Ag would ensure that host resources (APC, cytokines) for which T cells compete are devoted to T cells with the best effector potential. One implication is that favoring expansion of the fittest effector T cells in general may be more important than increasing the diversity of the T cell repertoire.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology*
  • Cell Proliferation
  • Epitopes / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • H-Y Antigen / immunology
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Immunodominant Epitopes / immunology*
  • Kinetics
  • Mice
  • Mice, Inbred Strains

Substances

  • Antibodies
  • Epitopes
  • Epitopes, T-Lymphocyte
  • H-Y Antigen
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunodominant Epitopes
  • hemagglutinin, avian influenza A virus