Affiliation:
1. Department of Microbiology-Immunology and Institute of Neuroscience, Northwestern University Medical School, Chicago, Illinois 60611
Abstract
ABSTRACT
The role of virus-specific cytotoxic T lymphocytes (CTL) in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease, a viral model for multiple sclerosis, is not yet clear. To investigate the specificity and function of CTL generated in response to TMEV infection, we generated a panel of overlapping 20-mer peptides encompassing the entire capsid and leader protein region of the BeAn strain of TMEV. Binding of these peptides to H-2K
b
and H-2D
b
class I molecules of resistant mice was assessed using RMA-S cells. Several peptides displayed significant binding to H-2K
b
, H-2D
b
, or both. However, infiltrating cytotoxic T cells in the central nervous system of virus-infected mice preferentially lysed target cells pulsed with VP2
111-130/121-140
or VP2
121-130
, a previously defined CTL epitope shared by the DA strain of TMEV and other closely related cardioviruses. In addition, at a high effector-to-target cell ratio, two additional peptides (VP2
161-180
and VP3
101-120
) sensitized target cells for cytolysis by infiltrating T cells or splenic T cells from virus-infected mice. The minimal epitopes within these peptides were defined as VP2
165-173
and VP3
110-120
. Based on cytokine profiles, CTL specific for these subdominant epitopes are Tc2, in contrast to CTL for the immunodominant epitope, which are of the Tc1 type. Interestingly, CTL function towards both of these subdominant epitopes is restricted by the H-2D molecule, despite the fact that these epitopes bind both H-2K and H-2D molecules. This skewing toward an H-2D
b
-restricted response may confer resistance to TMEV-induced demyelinating disease, which is known to be associated with the
H-2D
genetic locus.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Reference54 articles.
1. Allen, I., and B. Brankin. 1993. Pathogenesis of multiple sclerosis—the immune diathesis and the role of viruses. J. Neuropathol. Exp. Neurol. 52 : 95-105.
2. H-2D
b
−/−
Mice Are Susceptible to Persistent Infection by Theiler's Virus
3. Brain-infiltrating cytolytic T lymphocytes specific for Theiler's virus recognize H2Db molecules complexed with a viral VP2 peptide lacking a consensus anchor residue
4. Bureau, J. F., X. Montagutelli, F. Bihl, S. Lefebvre, J. L. Guenet, and M. Brahic. 1993. Mapping loci influencing the persistence of Theiler's virus in the murine central nervous system. Nat. Genet. 5 : 87-91.
5. Clatch, R. J., R. W. Melvold, S. D. Miller, and H. L. Lipton. 1985. Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease in mice is influenced by the H-2D region: correlation with TMEV-specific delayed-type hypersensitivity. J. Immunol. 135 : 1408-1414.
Cited by
38 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献