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 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.
Milner
Joshua D
JD
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. jdmilner@niaid.nih.gov
Fazilleau
Nicolas
N
McHeyzer-Williams
Michael
M
Paul
William
W
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D005434:Flow Cytometry; D015847:Interleukin-4 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4