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

Lecia Pewe; Stephen B. Heard; Conni Bergmann; Morris O Dailey; Stanley Perlman

doi:10.4049/jimmunol.163.11.6106

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

Journal article

Peer reviewed

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

Lecia Pewe, Stephen B. Heard, Conni Bergmann, Morris O Dailey and Stanley Perlman

Journal of immunology (Baltimore, Md. : 1950), Vol.163(11), pp.6106-6113

12/01/1999

DOI: 10.4049/jimmunol.163.11.6106

PMID: 10570300

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Abstract

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.

Demyelinating Diseases

Paralysis

T-Lymphocytes, Cytotoxic - immunology

Acute Disease

Viral Envelope Proteins - genetics

Mice, Inbred C57BL

Genes, T-Cell Receptor beta

Coronavirus Infections - immunology

Membrane Glycoproteins - genetics

Genetic Variation

Murine hepatitis virus - immunology

Spike Glycoprotein, Coronavirus

Animals

Immunoglobulin Variable Region - genetics

Viral Envelope Proteins - immunology

Mice

Receptors, Antigen, T-Cell - genetics

Membrane Glycoproteins - immunology

Chronic Disease

Encephalitis, Viral - immunology

Immunodominant Epitopes

Murine hepatitis virus - genetics

Details

Title: Subtitle: Selection of CTL escape mutants in mice infected with a neurotropic coronavirus: quantitative estimate of TCR diversity in the infected central nervous system
Creators: Lecia Pewe - University of Iowa
Stephen B. Heard
Conni Bergmann
Morris O Dailey
Stanley Perlman
Resource Type: Journal article
Publication Details: Journal of immunology (Baltimore, Md. : 1950), Vol.163(11), pp.6106-6113
DOI: 10.4049/jimmunol.163.11.6106
PMID: 10570300
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: AI43497 / NIAID NIH HHS NS36592 / NINDS NIH HHS AI22730 / NIAID NIH HHS
Language: English
Date published: 12/01/1999
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777478702771

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