Class II major histocompatibility complex restriction of human T cell responses to short ragweed allergen, Amb a V

AbstractAlthough T cells are known to play a crucial role in the induction of IgE synthesis, the class II major histocompatibility complex (MHC) restriction of aeroallergen‐induced T cell responses in humans is incompletely defined. We have previously shown that, in allergic Caucasoid individuals, HLA‐DR2 and Dw2 (DR2.2) is strongly associated with specific IgE and IgG antibody responses to highly purified Ambrosia (ragweed) allergen, Amb a V, from the artemisiifolia (short) species. For example, 95% of IgE antibody responders to Amb a V were typed as DR2.2. In a novel study of the genetic control of T cell responses to the Amb a V allergen, we have investigated the MHC class II restriction specificity of three CD4, Amb a V‐specific T cell clones derived from a DR2.2+ atopic patient, and a polyclonal Amb a V‐reactive T cell line from another DR2.2+ patient. We observed proliferative responses of all three clones to Amb a V only when either HLA‐DR2.2 or DR2, Dw12 (DR2.12; found on Mongoloid populations) was present on the antigen‐presenting cells, regardless of the HLA‐DQ phenotype of the cells. Moreover, the responses of T cell line and clones were abolished by anti‐DR but not by anti‐DQ nor by anti‐DP monoclonal antibodies, and, significantly, anti‐DRα/β12 (anti‐α/β1w15/w16; anti‐“DR2b”) monoclonal antibody blocked, in a dose‐dependent manner, the cloned T cell responses to Amb a V. These findings demonstrate that DRα/β12.2 (DRα/β11501) and DRα/β12.12 (DRα/β11502) are functional in the restriction of the T cell recognition of Amb a V. These findings also illustrate the power of the allergy model for definitive investigation of the molecular basis of the human immune response.