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Antigen specificity of CD4 T cell response in the central nervous system of mice infected with mouse hepatitis virus
Journal article   Open access   Peer reviewed

Antigen specificity of CD4 T cell response in the central nervous system of mice infected with mouse hepatitis virus

Shurong Xue and Stanley Perlman
Virology, Vol.238(1), pp.68-78
11/10/1997
DOI: 10.1006/viro.1997.8819
PMID: 9375010
url
https://doi.org/10.1006/viro.1997.8819View
Published (Version of record) Open Access

Abstract

Previously, we showed that the transmembrane (M) and surface (S) glycoproteins were recognized by splenic CD4 T lymphocytes harvested from mice infected intraperitoneally with mouse hepatitis virus, strain JHM (MHV-JHM), whereas only the S protein was recognized by splenocytes derived from mice with MHV-induced chronic demyelination. From these results, it could not be determined which proteins were recognized by T cells localized in the infected central nervous system (CNS). Herein, we show that CD4 T cells responding to both the M and S proteins can be detected in the CNS of mice with either acute encephalitis or the chronic demyelinating disease. As part of these analyses, two CD4 T cell epitope regions encompassing residues 328-347 and 358-377 within the S protein were identified. Both epitopes, as well as a previously identified M-specific epitope, were recognized by the CNS-derived lymphocytes. Finally, viral RNA harvested from mice with chronic demyelination was analyzed for mutations in the S specific CD4 T cell epitopes since changes resulting in escape from CD8 T cell surveillance were previously identified in these samples. A mutation in epitope region S(328-347) (ala to thr at position 337) was detected in a minority of samples but this change did not abrogate recognition of the epitope and therefore was unlikely to contribute to virus persistence. In conclusion, these studies identify epitopes recognized by MHV-specific CD4 T cells in the infected CNS and show that these cells are preferentially located at the site of infection in mice with clinical disease.
Lymphocyte Activation Demyelinating Diseases - virology Paralysis - immunology Lymphocyte Depletion Mice, Inbred Strains Coronavirus Infections - immunology Central Nervous System - immunology CD4-Positive T-Lymphocytes - immunology Epitopes - immunology Murine hepatitis virus - immunology Spike Glycoprotein, Coronavirus Antigens, Viral - immunology Animals Paralysis - virology Demyelinating Diseases - immunology Viral Envelope Proteins - immunology Mice Viral Matrix Proteins - immunology Membrane Glycoproteins - immunology Tumor Cells, Cultured RNA, Viral - isolation & purification Astrocytoma Central Nervous System - virology Interferon-gamma - biosynthesis

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