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

First Author  Lo WL Year  2014
Journal  Elife Volume  3
Pages  e01457 PubMed ID  24424413
Mgi Jnum  J:207985 Mgi Id  MGI:5560399
Doi  10.7554/eLife.01457 Citation  Lo WL, et al. (2014) T cell immunodominance is dictated by the positively selecting self-peptide. Elife 3:e01457
abstractText  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 V11alpha(+)Vbeta3(+), a major TCR pair in MCC-specific immunodominance. The gp250-selected V11alpha(+)Vbeta3(+) 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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