THE INFLUENCE OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II GENES AND T-CELL V-BETA REPERTOIRE ON RESPONSE TO IMMUNIZATION WITH HBSAG

Nonresponsiveness ro HBsAg vaccination is observed in 5-10% of vaccine recipients and is possibly caused by a defect in the T helper cell co mpartment. The immune response to HBsAg is influenced by genes of the major histocompatibility complex. We have investigated MHC class I and class II antigens in 53 adult responders and 73 nonresponders. Result s obtained in this first study were tested in a second study with 56 r esponders and 62 nonresponders from an infant vaccination trial. In ad dition, the peripheral V beta-chain T-cell receptor repertoire was inv estigated using monoclonal antibodies and flowcytometry in 26 adult re sponders and 38 nonresponders. As previously reported, nonresponsivene ss to HBsAg vaccination was associated with DRB13 and DRB1*7. In addi tion, DRB113 was significantly increased among vaccine responders (35 .2% vs 5.4%; p < 0.0001) suggesting an immune response promoting effec t for this allele whereas the closely related allele DRB114 was assoc iated with nonresponse in the infant study. There was no evidence for a hole in the T cell receptor V beta repertoire. In conclusion, in agr eement with results obtained in mice there appears to be a hierarchy o f DRB1 genes in the HBsAg immune response. The possible differential association of DRB113 and DRB1*14 may allow the identification of dif ferences between responsiveness and nonresponsiveness to a few amino a cid differences in the beta 1-domain of the class II heterodimer. (C) American Society for Histocompatibility and Immunogenetics, 1998. Publ ished by Elsevier Science Inc.