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Elife. 2014;3:e01457. doi: 10.7554/eLife.01457. Epub 2014 Jan 14.

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

Author information

1
Department of Immunology and Pathology, Washington University School of Medicine, St. Louis, United States.

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.

KEYWORDS:

MCC responses; immunodominance; positive selection; self-peptide

PMID:
24424413
PMCID:
PMC3885792
DOI:
10.7554/eLife.01457
[Indexed for MEDLINE]
Free PMC Article

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