Association of class II DNA restriction fragments with responsiveness to Ambrosia artemisiifolia (short ragweed)-pollen allergen Amb a V in ragweed-allergic patients

Abstract

Human IgE and IgG antibody responsiveness to the short ragweed-pollen allergen Amb a V (formerly known as Ra5) has been found to be strongly associated with HLA-D specificities Dw2 and DR2 in ragweed-allergic white individuals. To study the molecular basis of these associations, restriction fragment length polymorphism (RFLP) mapping was performed on a group of 45 white ragweed-allergic patients with full-length HLA-DR beta, DQ beta, and DQ alpha cDNA probes. The data on 41 of these subjects were used for the purposes of statistical analysis. With the DR beta probe, we found that the presence of three polymorphic restriction fragments correlated with responsiveness to Amb a V and with the DR2 specificity, namely, a 6.5 kb Eco RI fragment, a 9.4 kb Hind III fragment, and a 2.2 kb Hind III fragment. The presence of four fragments detected with the DQ beta probe correlated with responsiveness to Amb a V and with Dw2 specificity: a 2.3 kb Eco RI fragment, a 13.0 kb Pst I fragment, a 2.9 kb Taq I fragment, and a 5.2 kb Eco RV fragment. The DR beta Eco RI 6.5 kb and the DQ beta Eco RI 2.3 kb fragments were studied in detail; the concordant presence of these fragments was even more strongly associated with responsiveness to Amb a V. Fifteen of 17 responders had both fragments, whereas only one of 24 nonresponders had both fragments (p = 5 x 10(-7). This is the first time that such an association has been found between a person's immune response to a well-defined antigen and a set of HLA class II DNA restriction fragments.