The human immune response to hepatitis B surface antigen.
The anti-HBs response is bimodal with 4.2% of healthy persons producing no antibody and an additional 10% being hyporesponders. In the study of nonresponders, 2 extended haplotypes, [HLA-B8, SC01, DR3] and [HLA-B44, FC31, DR7], were found to be enriched in a pattern suggesting recessive inheritance. In the prospective immunization of homozygotes and heterozygotes for [HLA-B8, SC01, DR3], the homozygotes had less antibody than the heterozygotes. Family studies confirmed that the anti-HBs response was dominant and MHC linked, whereas nonresponse was recessive. In studies in vitro, it was shown that nonresponders failed to show lymphoproliferation in response to hepatitis B surface antigen (HBsAg) or an immunodominant nonapeptide. The lymphoproliferative response of responders to these stimuli was comparable and inhibited by anti-DR but not antibody to DQ or DP. The removal of CD8+ T cells did not produce lymphoproliferation to HBsAg in nonresponders. From mixtures of antigen-presenting cells and T cells from MHC-identical response discordant pairs, it was shown that the defect in the nonresponders was in their T cells and not their antigen-presenting cells, ruling out defective MHC binding or antigen processing as the basis of nonresponse.
Center for Blood Research, Harvard Medical School, Boston, Mass 02115, USA.
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D000818:Animals; D017951:Antigen Presentation; D017635:Clonal Anergy; D005799:Genes, Dominant; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D006510:Hepatitis B Antibodies / Q000096:biosynthesis* / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D008211:Lymphocyte Cooperation / Q000235:genetics; D051379:Mice; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000172:deficiency; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D006684:HLA-DR Antigens; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D016056:Immunodominant Epitopes; D011948:Receptors, Antigen, T-Cell