Genetic control of the immune response to hepatitis B surface antigen in humans

To investigate the HLA-linked genetic control of the human immune response, we immunized 339 healthy Japanese medical students with recombinant hepatitis B surface antigen and determined the HLA types by PCR-SSOP method. The anti-HBs antibody titers showed a log normal distribution, suggesting that the immune response to HBsAg in humans is a multifactorial and continuous trait. A stepwise multiple regression analysis demonstrated quantitatively how all loci of the HLA-class I (HLA-A and B) and class II (HLA-DRB1, DQA1, DQB1, DPA1, and DPB1) genes contributed to anti-HBs antibody production. The multiple correlation coefficient of antibody production to HBsAg with the DRB1 locus was 0.34, and it was highest among all the HLA loci. The incorporated correlation coefficients of class I and class II with the antibody production were 0.36 and 0.44, respectively, and that of the presence of entire HLA genes was 0.50, suggesting that the class I and class II loci within the HLA multigene family are dynamically involved in the regulation of the immune response to HBsAg. The predicting equation for anti-HBs antibody levels for the individuals with any HLA types was proposed by multiple regression analysis. Thus, we can predict anti-HBs titers of individuals by the HLA typing prior to immunization.