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. |