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T cell immunodominance is dictated by the positively selecting self-peptide.
Lo, Wan-Lin; Solomon, Benjamin D; Donermeyer, David L; Hsieh, Chyi-Song; Allen, Paul M.
Afiliación
  • Lo WL; Department of Immunology and Pathology, Washington University School of Medicine, St. Louis, United States.
Elife ; 3: e01457, 2014.
Article en En | MEDLINE | ID: mdl-24424413
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(+)Vß3(+), a major TCR pair in MCC-specific immunodominance. The gp250-selected V11α(+)Vß3(+) 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fragmentos de Péptidos / Receptores de Antígenos de Linfocitos T / Linfocitos T CD4-Positivos / Epítopos Inmunodominantes / Proteínas de Insectos / Citocromos c Límite: Animals Idioma: En Revista: Elife Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fragmentos de Péptidos / Receptores de Antígenos de Linfocitos T / Linfocitos T CD4-Positivos / Epítopos Inmunodominantes / Proteínas de Insectos / Citocromos c Límite: Animals Idioma: En Revista: Elife Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido