#49-OR
THE HOST POPULATION PERSPECTIVE IN PATHOGEN DEFENSE: CLUES FROM BORRELIA BURGDORFERI AND HLA.
W. Klitz , L.A. Baxter-Lowe and A. Steere . 1 Public Health, Univ Calif, Berkeley, CA ; 2 Immunogenetics, UCSF, CA and 3 Mass Gen Hops, Harvard Medical School, Boston, MA .
The adaptive immune system depends on HLA antigen presentation for activation. What is the allele-specific effectiveness of the HLA repertoire for announcing an infectious agent, and what portion of a population is able to respond through class II antigen presentation? Lyme arthritis is a good model to address these questions, because the T cell response to a single peptide of B. burgdorferi (OspA163-175) is significantly associated with the persistence of arthritis despite antibiotic therapy, called antibiotic-refractory Lyme arthritis.
Binding of the OspA163-175 peptide to 14 recombinant or purified DRB molecules was determined using an in vitro assay. Binding could be classified as strong, weak or absent.
European American Lyme arthritis patients (n=121) were classified as being either antibiotic-responsive or antibiotic-refractory. While the overall the frequency of DRB-DQA1-DQB1 haplotypes of the Lyme patient samples did not differ from a control population, overall differences between antibiotic-refractory or 
responsive patients were extremely significant.
When the in vitro binding assay results were compared to the frequency-deviant DRB alleles in the case-control study, the OpsA peptide binding alleles were the same as those over-represented in the antibiotic-refractory group, and the non-binding alleles were those under-represented. Interestingly, the common DRB1*1501 allele showed no binding, but DRB5*0101, expressed on the same haplotype, did bind the OspA peptide moderately well and was present in slight excess in the case-control study. Overall, we estimate that about 50% of DRB1 haplotypes, or 75% of the population, would have the capacity to present the OspA peptide.