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J Immunol. 2010 Jun 15;184(12):6569-73. doi: 10.4049/jimmunol.1000674. Epub 2010 May 21.

Cutting edge: lack of high affinity competition for peptide in polyclonal CD4+ responses unmasks IL-4 production.

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Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.


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 Vbeta3 transgenic mice, which have a fixed beta-chain specific for pigeon cytochrome c peptide I-Ek. Priming populations de-pleted of higher affinity, moth cytochrome c pep-tide I-Ek tetramer-binding cells resulted in substantial IL-4 production that did not occur in the presence of higher affinity cells. TCRalpha-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.

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