INDUCTION OF IL-4-PRODUCING CD4(-CELLS BY ANTIGENIC PEPTIDES ALTERED FOR TCR BINDING() T)

The adaptive immune responses to foreign Ags are primarily regulated b y the cytokines produced by CD4 T cells, The generation of distinct cy tokine-producing T cell subsets has been shown to be influenced by a n umber of factors, including cytokines, different types of APCs, and th e amounts of priming Ag, We have previously reported that the affinity of an antigenic peptide for its presenting MHC class II molecules and that different doses of Ag peptide affect the outcome of the function al CD4 T cell response, In the current study, we further examined the impact of the affinity of an antigenic peptide for its TCR on CD4 T ce ll priming, We generated a panel of Ag peptide variants mutated at pos itions known to be critical for binding to a well-characterized TCR (k nown as altered peptide ligands, or APLs), Compared with the WT peptid e, these APLs are defective in stimulating the proliferative responses of T cells, However, they can effectively prime in vitro naive CD4 T cells for differentiation into both Th1-like and Th2-like cells, In co ntrast, the WT peptide primes only for IFN-gamma-producing Th1-like ce lls, Using highly purified dendritic cells as APCs to present the APL or WT peptide leads to the same pattern of priming as using total sple nic APCs, These results indicate that priming by APLs for both IL-4 pr oduction and IFN-gamma production does not require two different types of APCs, In summary, our data indicate that APL can directly stimulat e naive CD4 T cells to become Th2 effector cells.