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

• Main Authors: Wan-Lin Lo, Benjamin D Solomon, David L Donermeyer, Chyi-Song Hsieh, Paul M Allen
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2014-01-01
• Series: eLife
• Subjects: positive selection; self-peptide; immunodominance; MCC response
• Online Access: https://elifesciences.org/articles/01457

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-Ek ligand to study the MCC highly organized immunodominance hierarchy. The single gp250/I-Ek 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.