PREDOMINANCE OF MHC CLASS II-RESTRICTED CD4(-CELLS AGAINST MOUSE HEPATITIS-VIRUS A59() CYTOTOXIC T)

Coronavirus-induced acute hepatitis is a complex event and the role of different components of the immune system with regard to defined vira l proteins and the course of the infection is not yet clear. We have a nalysed the cytotoxic T-lymphocyte (CTL) response in mouse hepatitis v irus (MHV-A59) infection. Surprisingly, we detected only a very clear virus-specific major histocompatibility complex (MHC) class II-restric ted cytotoxicity in mice infected with MHV-A59. We found no evidence o f activation of the classical CD8(+) MHC class I-restricted CTL. The v irus-specific CD4(+) CTL derived from two different mouse strains havi ng different MHC haplotypes recognized the same immunodominant epitope . This epitope, comprising the amino acid residues 329-343 of the vira l S-glycoprotein, was recognized both at the polyclonal level and by v irus-specific CTL clones. Transfer studies using a MHV-AS9-specifre CD 4(+) CTL done showed significant protection against a lethal challenge with MHV-A59, implicating that these CD4(+) CTL play a pivotal role i n the protection against MHV-A59 infections.