TY - JOUR
T1 - T cell immunodominance is dictated by the positively selecting self-peptide
AU - Lo, Wan Lin
AU - Solomon, Benjamin D.
AU - Donermeyer, David L.
AU - Hsieh, Chyi Song
AU - Allen, Paul M.
PY - 2014/1/14
Y1 - 2014/1/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84892621959&partnerID=8YFLogxK
U2 - 10.7554/eLife.01457.001
DO - 10.7554/eLife.01457.001
M3 - Article
C2 - 24424413
AN - SCOPUS:84892621959
VL - 2014
JO - eLife
JF - eLife
SN - 2050-084X
IS - 3
M1 - e01457
ER -