PMID- 9831134 OWN - NLM STAT- MEDLINE DCOM- 19990205 LR - 20190905 IS - 0198-8859 (Print) IS - 0198-8859 (Linking) VI - 59 IP - 12 DP - 1998 Dec TI - Binding specificity of a class II-restricted hepatitis B epitope by DR molecules from responder and nonresponder vaccine recipients. PG - 783-93 AB - A small but significant proportion of people who receive the hepatitis B vaccine do not produce anti-hepatitis B antibodies, a phenomenon associated with certain human leukocyte antigen (HLA) class II haplotypes. We were interested in determining whether natural allelic differences between two HLA-DR4 molecules associated with responder versus nonresponder subtypes differed with respect to binding of an immunodominant hepatitis B surface antigen (HBsAg) peptide as measured using a resonant mirror biosensor. In contrast to our original hypothesis, we found a ten-fold difference in the affinity in favor of the nonresponder DRB1*0401 allele, with a KD of 6.89 x 10(-8) M versus a KD of 6.71 x 10(-7) M for the responder DRB1*0404 allele. Half-times of dissociation were 1.3 min and 7.7 min, respectively, although association rate constants for both HLA class II molecules were similar (approximately 10(4) M(-1)s(-1)). Of particular interest was the observation of different on-rates during the association phase, suggesting that stoichiometry of binding was not 1:1 or that different structural forms of the HLA-peptide complex exist. Our observations indicate that whereas HBsAg peptide binding to HLA class II molecules is influenced by HLA polymorphism, the nonresponse to hepatitis B vaccine associated with this HLA-DR4 subtype is not a result of failure of processed HBsAg to bind HLA class II molecules. FAU - Schuenke, K W AU - Schuenke KW AD - Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA. FAU - Cook, R G AU - Cook RG FAU - Rich, R R AU - Rich RR LA - eng GR - R37 AI15394/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Hum Immunol JT - Human immunology JID - 8010936 RN - 0 (HLA-DR Antigens) RN - 0 (HLA-DR4 Antigen) RN - 0 (Hepatitis B Antibodies) RN - 0 (Hepatitis B Surface Antigens) RN - 0 (Hepatitis B Vaccines) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Immunodominant Epitopes) RN - 0 (Peptides) RN - 0 (Receptors, Antigen, T-Cell) SB - IM MH - Alleles MH - Biosensing Techniques MH - Cloning, Molecular MH - Enzyme-Linked Immunosorbent Assay MH - HLA-DR Antigens/immunology/*metabolism MH - HLA-DR4 Antigen/genetics/metabolism MH - Hepatitis B/*immunology/prevention & control MH - Hepatitis B Antibodies/blood MH - Hepatitis B Surface Antigens/immunology/*metabolism MH - Hepatitis B Vaccines/administration & dosage/*immunology MH - Histocompatibility Antigens Class II/genetics/isolation & purification MH - Histocompatibility Testing MH - Humans MH - Immunodominant Epitopes/*immunology/metabolism MH - Kinetics MH - Peptides/immunology/metabolism MH - Receptors, Antigen, T-Cell/immunology/metabolism MH - T-Lymphocytes/immunology EDAT- 1998/11/27 00:00 MHDA- 1998/11/27 00:01 CRDT- 1998/11/27 00:00 PHST- 1998/11/27 00:00 [pubmed] PHST- 1998/11/27 00:01 [medline] PHST- 1998/11/27 00:00 [entrez] AID - S0198-8859(98)00072-X [pii] AID - 10.1016/s0198-8859(98)00072-x [doi] PST - ppublish SO - Hum Immunol. 1998 Dec;59(12):783-93. doi: 10.1016/s0198-8859(98)00072-x.