T cell immunodominance is dictated by the positively selecting self-peptide

Elife. 2014;3:e01457. doi: 10.7554/eLife.01457. Epub 2014 Jan 14.

Abstract

Naive T cell precursor frequency determines the magnitude of immunodominance. While a broad T cell repertoire requires diverse positively selecting self-peptides, how a single positively selecting ligand influences naive T cell precursor frequency remains undefined. We generated a transgenic mouse expressing a naturally occurring self-peptide, gp250, that positively selects an MCC-specific TCR, AND, as the only MHC class II I-E(k) ligand to study the MCC highly organized immunodominance hierarchy. The single gp250/I-E(k) ligand greatly enhanced MCC-tetramer(+) CD4(+) T cells, and skewed MCC-tetramer(+) population toward V11α(+)Vβ3(+), a major TCR pair in MCC-specific immunodominance. The gp250-selected V11α(+)Vβ3(+) CD4(+) T cells had a significantly increased frequency of conserved MCC-preferred CDR3 features. Our studies establish a direct and causal relationship between a selecting self-peptide and the specificity of the selected TCRs. Thus, an immunodominant T cell response can be due to a dominant positively selecting self-peptide. DOI: http://dx.doi.org/10.7554/eLife.01457.001.

Keywords: MCC responses; immunodominance; positive selection; self-peptide.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Complementarity Determining Regions / genetics
  • Complementarity Determining Regions / immunology
  • Cytochromes c / genetics
  • Cytochromes c / immunology*
  • Cytochromes c / metabolism
  • H-2 Antigens / genetics
  • H-2 Antigens / immunology
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology
  • Immunodominant Epitopes / immunology*
  • Immunodominant Epitopes / metabolism
  • Insect Proteins / genetics
  • Insect Proteins / immunology*
  • Insect Proteins / metabolism
  • Ligands
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism

Substances

  • Complementarity Determining Regions
  • H-2 Antigens
  • Histocompatibility Antigens Class II
  • Immunodominant Epitopes
  • Insect Proteins
  • Ligands
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • Cytochromes c