Changes in the affinity of the interaction between T cell Ag receptors and their ligands can modulate selected T cell effector functions. Since both allergen-specific Th2 and Th0 cells are present in the peripheral CD4+ T cell pool of atopic individuals, the potential to inhibit cytokine production by Th2 cells and promote Th1-type cytokines from Th0 cells may contribute to the down-regulation of allergic inflammation. The aim of this study was to investigate the effects of peptide analogues of a dominant T cell epitope of the group II allergen derived from house dust mite, residues 28 to 40, on proliferation and cytokine production by human Th2 and Th0 cells. From both functional competition and proliferation assays, using analogues substituted with alanine or charged amino acids, the influence of different positions in p28-40 on TCR recognition and/or MHC class II binding was determined. For the specific Th0 cells, generally those analogues that lead to a reduction in proliferation also decreased both IL-4 and IFN-gamma production. However, the p28-40 analogues with alanine residues at positions 34 and 36 altered the IFN-gamma:IL-4 ratio by selectively enhancing IFN-gamma secretion. In the case of Th2 cells, stimulation with the peptide analogues induced different patterns of effector function. Selected analogues were capable of inducing IL-4 production in the absence of proliferation, whereas in response to other peptide variants of p28-40, both IL-4 production and proliferation were inhibited.