MOLECULAR ANALYSIS OF H INFLUENZAE RESPONSE

Scripps Research Institute, La Jolla CA

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Abstract

We hypothesized that the reason that Navajos and other genetically related individuals are 10-fold more susceptible to Haemophilus influenzae infection than other populations could be due to a polymorphism in one of the V genes in that pauciclonal response. We proposed that the A2 light chain gene might be the most critical, and suggested that Navajos might have a variant allele of the Vk gene A2. In this study, we also planned to determine how much non-random V gene usage there is at the level of V(D)J rearrangement, what factors influence non-equal gene rearrangement, how much initial junctional diversity is created, and how much selection acts upon the initial rearrangements. This information will allow us to test our hypothesis that the anti-Hib response is slow to arise in ontogency because the VkA2 gene will rearrange very infrequently, and that the Vk-Jk junction will only rarely be made.