Silencing an immunodominant epitope of hepatitis B surface antigen reveals an alternative repertoire of CD8 T cell epitopes of this viral antigen.
Immunodominance hierarchies operating in immune responses to viral antigens limit the diversity of the elicited T cell responses. The L(d)/S(28-39)-restricted CD8 T cell response to the hepatitis B surface antigen (HBsAg or S) prevents copriming of D(d)- and K(b)-restricted CD8 T cell responses. We exchanged L to V at position S(39) of HBsAg to construct mutant S(L39V). Comparable levels of wild-type S and mutant S(L39V) were produced by transiently transfected cells, and mice immunized with the pCI/S and pCI/S(L39V) DNA vaccines showed comparable serum antibody responses to HBsAg. The pCI/S but not pCI/S(L39V) DNA vaccination induced L(d)/S(28-39)-specific CD8 T cell responses. However, the pCI/S(L39V) DNA vaccine efficiently primed CD8 T cell responses to the subdominant D(d)- and K(b)-restricted epitopes, confirming the immunosuppressive phenotype of the L(d)/S(28-39)-specific CD8 T cell response. A single point mutation within the HBsAg can hence completely silence a 'dominant' CD8 T cell response thereby facilitating priming of a multispecific repertoire of suppressed, 'subdominant' epitopes. The data have practical implications for understanding HBV-specific CD8 T cell responses and for the design of novel vaccination strategies.
Wieland
Andreas
A
Department of Internal Medicine I, University Hospital of Ulm, Ulm, Germany.
Riedl
Petra
P
Reimann
Jörg
J
Schirmbeck
Reinhold
R
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017354:Point Mutation; D019444:Vaccines, DNA / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D016056:Immunodominant Epitopes; D019444:Vaccines, DNA