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Cytotoxic T cell-resistant variants are selected in a virus-induced demyelinating disease. Immunity 1996 Sep;5(3):253-62

Date

09/01/1996

Pubmed ID

8808680

DOI

10.1016/s1074-7613(00)80320-9

Scopus ID

2-s2.0-0030249395 (requires institutional sign-in at Scopus site)   83 Citations

Abstract

C57BI/6 mice infected with mouse hepatitis virus, strain JHM (MHV-JHM) develop a chronic demyelinating encephalomyelitis. Infectious virus can be isolated only from symptomatic mice. In C57BI/6 mice, two CD8+ T cell epitopes within the MHV-JHM surface glycoprotein were previously identified. Here, we show that mutations in the RNA encoding the immunodominant of the epitopes are present in nearly all virus samples isolated from these mice. Mutations are not present in sequences flanking this epitope or in other CD8+ or CD4+ T cell epitopes. Furthermore, analysis of five peptides corresponding to variant epitopes in direct ex vivo cytotoxicity assays showed that each mutation caused a loss of epitope recognition. These results suggest that escape from CD8+ T cell recognition is necessary for enhanced virus replication and development of clinical disease in these MHV-JHM-infected mice.

Author List

Pewe L, Wu GF, Barnett EM, Castro RF, Perlman S

Author

Edward M. Barnett MD, PhD Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Coronavirus Infections
Cytotoxicity, Immunologic
Demyelinating Diseases
Epitopes
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Murine hepatitis virus
Mutation
RNA, Viral
T-Lymphocytes, Cytotoxic