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Antibody-mediated protection against cytotoxic T-cell escape in coronavirus-induced demyelination
Journal article   Open access   Peer reviewed

Antibody-mediated protection against cytotoxic T-cell escape in coronavirus-induced demyelination

Ajai A Dandekar, Gary Jacobsen, Thomas J Waldschmidt and Stanley Perlman
Journal of virology, Vol.77(22), pp.11867-11874
11/2003
DOI: 10.1128/JVI.77.22.11867-11874.2003
PMCID: PMC254260
PMID: 14581523
url
https://europepmc.org/articles/pmc254260View
Published (Version of record) Open Access

Abstract

C57BL/6 (B6) mice infected with mouse hepatitis virus (MHV) strain JHM develop a clinically evident, demyelinating encephalomyelitis. Infectious virus can be isolated from the spinal cords of these mice and is invariably mutated in the immunodominant CD8 T-cell epitope recognized in this strain. We showed previously that these persistently infected mice did not mount a measurable serum anti-MHV neutralizing antibody response. Here we show that cytotoxic T-lymphocyte (CTL) escape was not detected in MHV-infected BALB/b mice (H-2(b) haplotype), even though the same CD8 T-cell epitopes were recognized as in B6 mice. BALB/b mice had 25-fold more MHV-specific antibody-secreting cells in the central nervous system, the site of infection, than B6 mice, suggesting that local production of anti-MHV antibody contributed to this absence of CTL escape. Additionally, administration of anti-MHV neutralizing antibody to infected B6 mice suppressed the development of CTL escape mutants. These findings indicate a key role for the anti-MHV antibody response in suppressing virus replication, thereby minimizing the emergence and competitive advantage of CTL escape mutants.
T-Lymphocytes, Cytotoxic - immunology Animals Antibody-Producing Cells - physiology B-Lymphocytes - immunology Spleen - immunology Demyelinating Diseases - immunology Immunization, Passive Antibodies, Viral - immunology Mice Mice, Inbred BALB C Brain - immunology Murine hepatitis virus

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