TY - JOUR
T1 - Changing immunodominance patterns in antiviral CD8 T-cell responses after loss of epitope presentation or chronic antigenic stimulation
AU - Van Der Most, Robbert G.
AU - Murali-Krishna, Kaja
AU - Lanier, J. Gibson
AU - Wherry, E. John
AU - Puglielli, Maryann T.
AU - Blattman, Joseph N.
AU - Sette, Alessandro
AU - Ahmed, Rafi
N1 - Funding Information:
We thank Patryce Yeiser and Madhavi Krishna for technical assistance and Dr. Rob de Boer for stimulating discussions. This work was supported by National Institute of Health Grant AI30048 (to R.A.) and by a Cancer Research Institute postdoctoral fellowship (to E.J.W.).
PY - 2003/10/10
Y1 - 2003/10/10
N2 - The H-2b-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.
AB - The H-2b-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.
KW - Antigen presentation
KW - CD8 T cell
KW - Immunodomination
KW - LCMV
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U2 - 10.1016/j.virol.2003.07.001
DO - 10.1016/j.virol.2003.07.001
M3 - Article
C2 - 14592762
AN - SCOPUS:0242300038
SN - 0042-6822
VL - 315
SP - 93
EP - 102
JO - Virology
JF - Virology
IS - 1
ER -