+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Selection of CTL escape mutants in mice infected with a neurotropic coronavirus: quantitative estimate of TCR diversity in the infected central nervous system



Selection of CTL escape mutants in mice infected with a neurotropic coronavirus: quantitative estimate of TCR diversity in the infected central nervous system



Journal of Immunology 163(11): 6106-6113



Variant viruses mutated in the immunodominant cytotoxic T cell epitope surface (S) glycoprotein S-510-518 are selected in mice chronically infected with mouse hepatitis virus, strain JHM. We determined whether this selection occurred in the presence of an oligoclonal or polyclonal T cell response using soluble MHC/peptide tetramers in direct ex vivo analyses of CNS-derived lymphocytes. A total of 42% (range, 29-60%) of CD8 T cells in the CNS of mice with acute encephalitis recognized epitope S-510-518. A total of 34% (range, 18-62%) of cells from mice with hind limb paralysis (and chronic demyelination) were also epitope specific, even though only virus expressing mutated epitope is detected in these animals. Sequence analysis of the beta-chain CDR3 of 487 tetramer S-510-518-positive cDNA clones from nine mice showed that a majority of clonotypes were identified in more than one mouse. From these analyses, we estimated that 300-500 different CD8 T cell clonotypes responsive to epitope S-510-518 were present in each acutely infected brain, while 100-900 were present in the CNS of each mouse with chronic disease. In conclusion, a polyclonal CD8 T cell response to an epitope does not preclude the selection of T cell escape mutants, and epitope-specific T cells are still present at high levels even after RNA-encoding wild-type sequence is no longer detectable.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 018109690

Download citation: RISBibTeXText

PMID: 10570300


Related references

Infection with cytotoxic T-lymphocyte escape mutants results in increased mortality and growth retardation in mice infected with a neurotropic coronavirus. Journal of Virology 72(7): 5912-5918, 1998

Differential antigen recognition by T cells from the spleen and central nervous system of coronavirus-infected mice. Virology 222(1): 247-251, 1996

Regional localization of virus in the central nervous system of mice persistently infected with murine coronavirus JHM. Virology 166(2): 328-338, 1988

Effects of an epitope-specific CD8+ T-cell response on murine coronavirus central nervous system disease: protection from virus replication and antigen spread and selection of epitope escape mutants. Journal of Virology 78(3): 1150-1159, 2004

High-magnitude, virus-specific CD4 T-cell response in the central nervous system of coronavirus-infected mice. Journal of Virology 75(6): 3043-3047, 2001

Electron microscopy of central nervous system organotypic cultures infected with neurotropic viruses. Ultramicroscopy 19(4): 388-0, 1986

Quantitative variation of free amino acids in the central nervous system of MoMuLV-ts1-infected mice. In Vivo 12(4): 395-401, 1998

Bystander CD4 T cells do not mediate demyelination in mice infected with a neurotropic coronavirus. Journal of Neuroimmunology 137(1-2): 42-50, 2003

Demyelination is mediated by gamma-delta T cells in mice infected with a neurotropic coronavirus. Journal of Neurovirology 8(Suppl. 1): 31, 2002

Activation of astrocytes in the spinal cord of mice chronically infected with a neurotropic coronavirus. Virology 213(2): 482-493, 1995

Phenotypic and functional characterization of CD4+ T-cells infiltrating the central nervous system of rats infected with coronavirus MHV IV. Advances in Experimental Medicine and Biology 342: 437-442, 1993

Cutting edge: CD8 T cell-mediated demyelination is IFN-c dependent in mice infected with a neurotropic coronavirus. Journal of Immunology 168(4): 47-51, 2002

Depletion of blood-borne macrophages does not reduce demyelination in mice infected with a neurotropic coronavirus. Journal of Virology 73(8): 6327-6334, 1999

Interplay of complement and Fc receptors in antibody-induced demyelination in mice infected with a neurotropic coronavirus. FASEB Journal 18(4-5): Abst 778 3, 2004