Immune responsiveness to Ambrosia artemishfolia (short ragweed) pollen allergen Amb a VI (Ra6) is associated with HLA-DR5 in allergic humans

David G. Marsh, Linda R. Freidhoff, Eva Ehrlich-Kautzky, Wilma B. Bias, Marianne Roebber

The relationship between HLA type and specific immune responsiveness toward ultrapure Ambrosia artemisiifolia (short ragweed) pollen allergen Amb a VI (Ra6) was explored in a genetic-epidemiologic study of groups of 116 and 81 Caucasoid subjects who were skin-test positive (ST+) toward common environmental allergens. Specific immune responsiveness to Amb a VI was assessed by measuring serum IgE and IgG antibodies (Abs) by double Ab radioimmunoassay in both ST+ groups. Significant associations were found between IgE Ab responsiveness to Amb a VI and the possession of HLA-DR5; P values for the two groups were, respectively, 7 X 10(-7) and 1 X 10(-3) by nonparametric analyses, and 4 X 10(-11) and 5 X 10(-8) by parametric analyses. The levels of significance for the associations between HLA-DR5 and IgG Ab responsiveness were highly dependent on the extent of ragweed immunotherapy (Rx) within the patient group; by parametric statistics, the associations were 10(-11) for the group that had received relatively little Rx and 2 X 10(-3) for the group that had received more intensive Rx. These results provide further striking evidence for the existence of specific HLA-linked human Ir genes involved in responsiveness toward inhaled allergens and illustrate the usefulness of the allergy model in studies of the genetic basis of human immune responsiveness. Extension of these studies to investigation of structure-function relationships involved in antigen recognition by Ia molecules and the T-cell receptor will lead to a better understanding of human susceptibility toward immunologic diseases.