Binding specificity of a class II-restricted hepatitis B epitope by DR molecules from responder and nonresponder vaccine recipients.
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.
Schuenke
K W
KW
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
Cook
R G
RG
Rich
R R
RR
D000483:Alleles; D015374:Biosensing Techniques; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism*; D015804:HLA-DR4 Antigen / Q000235:genetics / Q000378:metabolism; D006509:Hepatitis B / Q000276:immunology* / Q000517:prevention & control; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000276:immunology / Q000378:metabolism*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000302:isolation & purification; D006650:Histocompatibility Testing; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology* / Q000378:metabolism; D007700:Kinetics; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D006684:HLA-DR Antigens; D015804:HLA-DR4 Antigen; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D010455:Peptides; D011948:Receptors, Antigen, T-Cell