CONTRIBUTION OF HLA CLASS-I AND CLASS-II ALLELES TO THE REGULATION OFANTIBODY-PRODUCTION TO HEPATITIS-B SURFACE-ANTIGEN IN HUMANS

The HLA multigene family consists of HLA class I (HLA-A, a and C) and class II (HLA-DR, DQ and DP) genes, and plays a central role in the re gulation of immune response, To investigate how each HLA gene and each HLA allele contribute to the human immune response, we immunized 339 healthy Japanese medical students with recombinant hepatitis B surface antigen (rHBsAg) and determined the HLA types of all vaccinated subje cts at the DNA level, The anti-HBs antibody titers showed a log-normal distribution, implying that the immune response to HBsAg in humans is a multifactorial and continuous trait, A stepwise multiple regression analysis demonstrated the alleles at the HLA-class I (HLA-A and B) an d class II (HLA-DRB1, DQA1, DQB1, DPA1 and DPB1) loci significantly co ntributed to antibody production to HBsAg, The predicting equation of anti-HBs antibody levels for individuals with any HLA phenotype was pr oposed based on a multiple regression analysis. The multiple correlati on coefficient of antibody production to HBsAg with the HLA-DRB1 locus was highest (0.34) among all of the HLA loci, whereas those with whol e HLA class I or class II loci were 0.36 or 0.44 respectively, The inc orporated correlation coefficient of the presence of all HLA gene fami lies with antibody production became 0.50, suggesting that HLA class I and class II loci within the HLA multigene family are dynamically inv olved in regulation of the immune response to HBsAg.