Haplotypes comprising subtypes of the DQB1*06 allele direct the antibody response after immunisation with hepatitis B surface antigen.

Two HLA class II haplotypes, HLA-[DQB10602; DQA10102; DR15] and HLA-[DQB10603; DQA10103; DRB11301] were found to be less common in 52 nonresponders compared with 68 responders, P<0.025 and P<0.05 respectively, after vaccination with hepatitis B surface antigen (HBsAg). Another haplotype, HLA-[DQB10604; DQA10102; DRB11302], had a significantly higher frequency in the nonresponders (P<0.005). The nonresponders and responders were nonsmoking, healthy individuals with an antibody concentration of <10 IU/l and >100 IU/l respectively. The three haplotypes comprise either of three different DQB106 subtypes. Two of the seven amino acids that differ between the two responder alleles DQB10602 and 0603 and the nonresponder allele 0604 are located in the peptide-binding groove of the DQB1 molecule. In addition to this finding, amino acid 86 in the DRB1 molecule seems to determine the response against HBsAg. DRB11301 and DR15 in the responder haplotypes have a Val at this position while the nonresponder haplotype has a Gly. These results suggest a role for both the DQB106 alleles and the DRB1 alleles *1301, *1302 and DR15 to direct either a response or a nonresponse against HBsAg. Sixteen HLA class II genotypes were found to be shared by 25 nonresponders and 32 responders. This finding of HLA-identical nonresponders and responders indicates an influence of other genetic factors in addition to the HLA system in the response to HBsAg.