Non-responsiveness to hepatitis B surface antigen vaccines is not caused by defective antigen presentation or a lack of B7 co-stimulation.
The mechanisms causing non-responsiveness to hepatitis B surface antigen (HBsAg) vaccines in man remain elusive. The increased incidence of non-responsiveness in subjects with HLA-DR3(+) or -DR7(+) haplotypes suggests that immune response mechanisms governed by genes of the MHC are involved. Homozygotes for these two haplotypes are found almost exclusively in the non-responder (NR) population. It is conceivable that antigen-presenting cells (APC) of NR are defective in the uptake of HBsAg and that they are unable to present this Ag adequately. Previously, we demonstrated that DR2(+), DR7(+) and DP4(+) NR were able to present HBsAg. In the present paper we demonstrate that six DR0301(+) NR, five of which are homozygous for this marker, were able to take up, process and present HBsAg to HBsAg-specific, DR0301-restricted T cell lines. Non-fractionated peripheral blood mononuclear cells (PBMC) from the DR0301(+) NR did not proliferate to HBsAg in vitro, whereas they proliferated vigorously upon stimulation with tetanus toxoid, thus ruling out the presence of a generalized immunodeficiency. We therefore conclude that HLA-DR0301(+) NR vaccinees are not deficient in their HBsAg-presentation. Because it was demonstrated that recently activated T cells can apparently bypass the requirement for B7, we may have overlooked the role of the B7-co-stimulation in our set-up that used HBsAg-specific T cell lines. Therefore we examined the expression of B7 co-stimulatory molecules on NR-APC. CD86 was normally present on these cells and was not down-regulated after culturing the PBMC in the presence of HBsAg. We conclude that CD86 expression on CD14(+) monocytes of DR0301- and DR07-homozygous poor responders is not deficient and cannot be the mechanism underlying the non-responsiveness of these subjects.
Desombere
I
I
Center for Vaccinology, Ghent University and Hospital, Ghent, Belgium. Isabelle.desombere@ugent.be
Cao
T
T
Gijbels
Y
Y
Leroux-Roels
G
G
D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D002460:Cell Line; D018920:Coculture Techniques / Q000379:methods; D006682:HLA-DP Antigens / Q000276:immunology; D059868:HLA-DP beta-Chains; D006684:HLA-DR Antigens / Q000276:immunology; D015803:HLA-DR3 Antigen; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C500433:HLA-DPB1*02:01 antigen; D006684:HLA-DR Antigens; C500432:HLA-DR0301 antigen; D015803:HLA-DR3 Antigen; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins