Binding specificity of a class II-restricted hepatitis B epitope by DR molecules from responder and nonresponder vaccine recipients

Hum Immunol. 1998 Dec;59(12):783-93. doi: 10.1016/s0198-8859(98)00072-x.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Biosensing Techniques
  • Cloning, Molecular
  • Enzyme-Linked Immunosorbent Assay
  • HLA-DR Antigens / immunology
  • HLA-DR Antigens / metabolism*
  • HLA-DR4 Antigen / genetics
  • HLA-DR4 Antigen / metabolism
  • Hepatitis B / immunology*
  • Hepatitis B / prevention & control
  • Hepatitis B Antibodies / blood
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B Surface Antigens / metabolism*
  • Hepatitis B Vaccines / administration & dosage
  • Hepatitis B Vaccines / immunology*
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / isolation & purification
  • Histocompatibility Testing
  • Humans
  • Immunodominant Epitopes / immunology*
  • Immunodominant Epitopes / metabolism
  • Kinetics
  • Peptides / immunology
  • Peptides / metabolism
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / immunology


  • HLA-DR Antigens
  • HLA-DR4 Antigen
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Histocompatibility Antigens Class II
  • Immunodominant Epitopes
  • Peptides
  • Receptors, Antigen, T-Cell