CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX RESTRICTION OF HUMAN T-CELL RESPONSES TO SHORT RAGWEED ALLERGEN, AMB-A-V

Although 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-DR-alpha/beta-I2 (anti-DR-alpha/beta-I(w)15/w16; anti-"DR2b") monoclonal antibody blocked, in a dose-dependent manner, the cloned T cell responses to Amb a V. These findings demonstrate that DR-alpha/beta-I2.2 (DR-alpha/beta-I1501) and DR-alpha/beta-I2.12 (DR-alpha/beta-I1502) 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.