The influence of major histocompatibility complex class II genes and T-cell Vbeta repertoire on response to immunization with HBsAg.
Nonresponsiveness to HBsAg vaccination is observed in 5-10% of vaccine recipients and is possibly caused by a defect in the T helper cell compartment. The immune response to HBsAg is influenced by genes of the major histocompatibility complex. We have investigated MHC class I and class II antigens in 53 adult responders and 73 nonresponders. Results obtained in this first study were tested in a second study with 56 responders and 62 nonresponders from an infant vaccination trial. In addition, the peripheral Vbeta-chain T-cell receptor repertoire was investigated using monoclonal antibodies and flow-cytometry in 26 adult responders and 38 nonresponders. As previously reported, nonresponsiveness to HBsAg vaccination was associated with DRB1*3 and DRB1*7. In addition, DRB1*13 was significantly increased among vaccine responders (35.2% vs 5.4%;p < 0.0001) suggesting an immune response promoting effect for this allele whereas the closely related allele DRB1*14 was associated with nonresponse in the infant study. There was no evidence for a hole in the T cell receptor Vbeta repertoire. In conclusion, in agreement with results obtained in mice there appears to be a hierarchy of DRB1* genes in the HBsAg immune response. The possible differential association of DRB1*13 and DRB1*14 may allow the identification of differences between responsiveness and nonresponsiveness to a few amino acid differences in the beta1-domain of the class II heterodimer.
Höhler
T
T
I. Department of Internal Medicine, Johannes Gutenberg University Mainz, Germany. hoehler@goofy.zdv.uni-mainz.de
Meyer
C U
CU
Notghi
A
A
Stradmann-Bellinghausen
B
B
Schneider
P M
PM
Starke
R
R
Zepp
F
F
Sänger
R
R
Clemens
R
R
Meyer zum Büschenfelde
K H
KH
Rittner
C
C
D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000276:immunology; D005787:Gene Frequency; D005802:Genes, MHC Class II; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007223:Infant; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*
D015721:Diphtheria-Tetanus-Pertussis Vaccine; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D016693:Receptors, Antigen, T-Cell, alpha-beta