Hepatitis B surface antigen presentation and HLA-DRB1*- lessons from twins and peptide binding studies.
The aim of this study was to investigate the underlying mechanisms of the genetic association between certain HLA-DRB1* alleles and the immune response to HBsAg vaccination. Therefore, HBsAg peptide binding to HLA-DR molecules was measured in vitro by peptide binding ELISAs. Additionally, HBsAg-specific T cell reaction and cytokine profile of immune response were analysed ex vivo in ELISPOT assays and DR-restriction of T-cell proliferative responses was investigated with HBsAg specific T cell clones. In addition, we compared HBsAg specific T cell responses of 24 monozygotic and 3 dizygotic twin pairs after HBsAg vaccination. Our results showed that the peptide binding assays did not reflect antigen presentation in vivo. DR alleles associated with vaccination failure like DRB1*0301 and 0701 efficiently presented HBsAg peptides. In 11 of 24 investigated monozygotic twin pairs we observed pronounced differences in the recognition of HBsAg peptides. This study indicates that HLA-DR associations with HBsAg vaccination response are not caused by differences in peptide binding or by a shift in the Th1/Th2 profile. Our findings strongly argue for differences in the T cell recognition of peptide/MHC complexes as the critical event in T cell responsiveness to HBsAg.
Kruger
A
A
Institute for Legal Medicine, Johannes Gutenberg University, Mainz, Germany. kruger@uni-mainz.de
Adams
P
P
Hammer
J
J
Böcher
W O
WO
Schneider
P M
PM
Rittner
C
C
Hoehler
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000915:Antibody Affinity; D017951:Antigen Presentation; D001667:Binding, Competitive; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D059811:HLA-DRB1 Chains; D006514:Hepatitis B Surface Antigens / Q000276:immunology* / Q000378:metabolism; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D008969:Molecular Sequence Data; D018417:Th1 Cells / Q000276:immunology; D014427:Twins / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines