title: T cell immunodominance is dictated by the positively selecting self-peptide.
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.
authors.affiliation: Department of Immunology and Pathology, Washington University School of Medicine, St. Louis, United States.
authors.forename: Wan-Lin
authors.initials: WL
authors.lastname: Lo
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Solomon
authors.forename: David L
authors.initials: DL
authors.lastname: Donermeyer
authors.forename: Chyi-Song
authors.initials: CS
authors.lastname: Hsieh
authors.forename: Paul M
authors.initials: PM
authors.lastname: Allen
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology; D045304:Cytochromes c / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology* / Q000378:metabolism; D019476:Insect Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism
chemical_list: D022801:Complementarity Determining Regions; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D019476:Insect Proteins; D008024:Ligands; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D045304:Cytochromes c
keywords: MCC responses; immunodominance; positive selection; self-peptide