Prevalent class I-restricted T-cell response to the Theiler's virus epitope Db:VP2121-130 in the absence of endogenous CD4 help, tumor necrosis factor alpha, gamma interferon, perforin, or costimulation through CD28.
C57BL/6 mice mount a cytotoxic T-lymphocyte (CTL) response against the Daniel's strain of Theiler's murine encephalomyelitis virus (TMEV) 7 days after infection and do not develop persistent infection or the demyelinating syndrome similar to multiple sclerosis seen in susceptible mice. The TMEV capsid peptide VP2121-130 sensitizes H-2Db+ target cells for killing by central-nervous-system-infiltrating lymphocytes (CNS-ILs) isolated from C57BL/6 mice infected intracranially. Db:VP2121-130 peptide tetramers were used to stain CD8(+) CNS-ILs, revealing that 50 to 63% of these cells bear receptors specific for VP2121-130 presented in the context of Db. No T cells bearing this specificity were found in the cervical lymph nodes or spleens of TMEV-infected mice. H-2(b) mice lacking CD4, class II, gamma interferon, or CD28 expression are susceptible to persistent virus infection but surprisingly still generate high frequencies of CD8(+), Db:VP2121-130-specific T cells. However, CD4-negative mice generate a lower frequency of Db:VP2121-130-specific T cells than do class II negative or normal H-2(b) animals. Resistant tumor necrosis factor alpha receptor I knockout mice also generate a high frequency of CD8(+) CNS-ILs specific for Db:VP2121-130. Furthermore, normally susceptible FVB mice that express a Db transgene generate Db:VP2121-130-specific CD8(+) CNS-ILs at a frequency similar to that of C57BL/6 mice. These results demonstrate that VP2121-130 presented in the context of Db is an immunodominant epitope in TMEV infection and that the frequency of the VP2121-130-specific CTLs appears to be independent of several key inflammatory mediators and genetic background but is regulated in part by the expression of CD4.
Johnson
A J
AJ
Departments of Immunology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Njenga
M K
MK
Hansen
M J
MJ
Kuhns
S T
ST
Chen
L
L
Rodriguez
M
M
Pease
L R
LR
D000818:Animals; D018106:CD28 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002213:Capsid / Q000276:immunology*; D036022:Capsid Proteins; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D017945:Theilovirus / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D018106:CD28 Antigens; D036022:Capsid Proteins; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D014409:Tumor Necrosis Factor-alpha; C442556:VP2 protein, Theilovirus; D054353:Perforin; D007371:Interferon-gamma