Prevalent class I-restricted T-cell response to the Thelier's virus epitope D-b : VP2(121-130) 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 Dani el's strain of Theiler's murine encephalomyelitis virus (TMEV) 7 days after infection and do not develop persistent infection or the demyelinating syn drome similar to multiple sclerosis seen in susceptible mice. The TMEV caps id peptide VP2(121-130) sensitizes H-2D(b+) target cells for killing by cen tral-nervous-system-infiltrating lymphocytes (CNS ILs) isolated from C57BL/ 6 mice infected intracranially, D-b:VP2(121-130) peptide tetramers were use d to stain CD8(+) CNS-ILs, revealing that 50 to 63% of these cells bear rec eptors specific for VP2(121-130) presented in the context of D-b. No T cell s bearing this specificity were found in the cervical lymph nodes or spleen s of TMEV-infected mice, H-2(b) mice lacking CD4, class II, gamma interfero n, or CD28 expression are susceptible to persistent virus infection but sur prisingly still generate high frequencies of CD8(+), D-b:VP2(121-130)-speci fic T cells. Holt ever, CD4-negative mice generate a lower frequency of D-b :VP2(121-130)-specific T cells than do class II negative or normal H-2(b) a nimals. Resistant tumor necrosis factor alpha receptor I knockout mice also generate a high frequency of CD8(+) CNS-ILs specific for D-b:VP2(121-130). Furthermore, normally susceptible FVB mice that express a D-b transgene ge nerate D-b:VP2(121-130)-specific CD8(+) CNS-ILs at a frequency similar to t hat of C57BL/6 mice. These results demonstrate that VP2(121-130) presented in the context of D-b is an immunodominant epitope in TMEV infection and th at the frequency of the VP2(121-130)-specific CTLs appears to be independen t of several key inflammatory mediators and genetic background but is regul ated in part by the expression of CD4.