Changing immunodominance patterns in antiviral CD8 T-cell responses after loss of epitope presentation or chronic antigenic stimulation.
The H-2(b)-restricted CD8 T-cell response against lymphocytic choriomeningitis virus is directed against at least 10 dominant and subdominant epitopes, including two newly identified epitopes in the nucleoprotein. We have used this set of epitopes to characterize the plasticity of the hierarchy under different experimental circumstances, i.e., loss of MHC class I molecules, loss of specific epitopes (CTL escape), and prolonged antigenic stimulation (chronic infection). We found that loss of epitope-specific responses was almost inevitably associated with compensatory responses against other, subdominant, epitopes. Multiple epitope loss was required to change the hierarchy. Persistent viral infection was associated with a loss of not only the dominant response against the NP396 epitope, but also a loss of subdominant responses against nucleoprotein epitopes. In contrast, responses against glycoprotein epitopes, dominant and subdominant, survived under chronic infection conditions, and even dominated the response (GP118). Our results suggest that the fate of each specific T-cell response during chronic infection is in part determined by the origin of the cognate epitopes, i.e, the proteins from which they are processed, or, more specifically, nucleoprotein versus glycoprotein. A model in which recruitment time plays a role in the longevity of antiviral T-cell responses during persistent infection is discussed.
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA. r.g.vandermost@vet.uu.nl
Robbert G
RG
van der Most
Kaja
K
Murali-Krishna
J Gibson
JG
Lanier
E John
EJ
Wherry
Maryann T
MT
Puglielli
Joseph N
JN
Blattman
Alessandro
A
Sette
Rafi
R
Ahmed
D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology*; D007156:Immunologic Memory; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D016056:Immunodominant Epitopes; D009698:Nucleoproteins