How the MHC selects Th1/Th2 immunity

While the effects of cytokines on T helper 1 (Th1)/Th2 differentiation are well documented, it is less clear why a dichotomy of effector cytokine production would initiate from antigen-specific lymphocytes. Nevertheless, in defined experimental systems, the interaction between T-cell receptor (TCR), peptide and major histocompatibility complex (MHC) can determine Th1/Th2 dominance. Here, Joseph Murray discusses how TCR affinity and ligand density might interface with innate forces in the selection of CD4+ T-cell functions.