The Density of the Class II MHC T Cell Receptor Ligand Influences IFN-γ/IL-4 Ratios in Immune Responsesin Vivo

Activation of CD4+T cells depends on T cell receptor recognition of MHC class II/peptide and on costimulation provided by CD28/B7. It has been shown that different levels of costimulation can influence T helper cell differentiation into Th1 versus Th2 phenotypes. Similar arguments have been made for different levels of peptide/MHC density on antigen-presenting cells, but to date supportive evidence has only come fromin vitrostudies. Here, using transgenic mice with reduced MHC class II expression on both B cells and dendritic cells, we demonstrate that T helper cell differentiationin vivois also influenced by the density of expression of MHC class II. Although priming and expansion of antigen-specific T cells were normal in these mice, T cell responses were dominated by the Th1-associated cytokine IFN-γ, with reduced levels of the Th2 cytokine IL-4 compared to controls. These results provide direct evidence that the efficiency of antigen presentationin vivocan determine effector cell phenotype.