Family studies of association between HLA and specific immune responses to highly purified pollen allergens

In 76 members of 13 large families, we investigated whether association exists between specific familialHLA haplotypes and immune responsiveness to four different highly purified pollen antigens (ragweed antigens E, Ra3, and Ra5 and rye grass Group I). Specific immune response was studied quantitatively by measurement of IgE-mediated skin sensitivity, serum IgG antibody, and antigen-induced lymphocyte proliferationin vitro. We found no evidence for association between specificHLA haplotype and specific response measured by any one or more of our indices of immune function. In several families we found evidence of specific response in one generation but not in another. We found a number of instances of individuals exhibiting lymphocyte responsiveness to an antigen, but no detectable specific IgE or IgG antibody. Surprisingly, we also found a few cases of individuals with marked IgE and/or IgG responses to a given antigen who showed no measurable lymphocyte responsiveness to that antigen, despite lymphocyte responsiveness to other nonimmunologically crossreacting antigens. In several cases, we also observed lymphocyte stimulation and serum IgG antibody, but no detectable IgE response. Our results conflict with previous investigators' reports of linkage betweenHLA haplotype and specific IgE-mediated skin sensitivity in families.HLA- linked immune response (Ir) loci may exist in humans, but genetic complexity and the limits of current technology preclude our ability to demonstrate their existence.