Selecting dominance

The precise extent to which thymic positive selection influences the subsequent immundominance hierachy of T cell antigen receptors (TCRs) is unclear. In eLife, Allen and colleagues investigate this by generating a mouse line (gp250 SC) that expresses a single CD4⁺ T cell–selecting ligand in the thymus that consists of the self gp250 peptide presented by I-E^k. 'Normal' mice primed by the nominal foreign antigen MCC generate a consistent and discrete TCR immundominance hierachy, and the gp250 peptide is able to positively select the most immunodominant TCR (V_α11⁺V_β3⁺) in these mice. The gp250 SC mice produce a diverse TCR repertoire but have a much higher frequency of CD4⁺ cells able to recognize MCC-derived peptides and have a TCR dominance hierachy similar to that of 'normal' mice primed with MCC. Furthermore, amino acid residues in complementarity-determining region 3 of the gp250 SC TCR show skewing toward recognition of MCC. These data demonstrate that a positively selecting ligand can directly determine the nature of the immunodominant T cell response.

eLife 110, 20176–20181 (2014)