Cutting Edge: Lack of High Affinity Competition for Peptide in Polyclonal CD4+ Responses Unmasks IL-4 Production

Priming of naive monoclonal CD4 T cells via weak agonsim permits GATA-3 transcription and Th2 differentiation. To test whether this process can occur in polyclonal naive populations, where a range of TCR affinities exists for any given Ag/MHC complex, we primed naive CD4 cells from 5CC7 V beta 3 transgenic mice, which have a fixed beta-chain specific for pigeon cytochrome c peptide I-E-k. Priming populations depleted of higher affinity, moth cytochrome c peptide I-E-k tetramer-binding cells resulted in substantial IL-4 production that did not occur in the presence of higher affinity cells. TCR alpha-chain sequence analysis showed that clones that possessed TCR features associated with high affinity responses to pigeon cytochrome c made less IL-4 than clones that possessed fewer such motifs. These results indicate that cells bearing TCRs that are weakly stimulated by their cognate Ag preferentially adopt a Th2 phenotype when primed in the absence of competition from cells with higher affinity receptors. The Journal of Immunology, 2010, 184: 6569-6573.