PROTECTIVE IMMUNITY DOES NOT CORRELATE WITH THE HIERARCHY OF VIRUS-SPECIFIC CYTOTOXIC T-CELL RESPONSES TO NATURALLY PROCESSED PEPTIDES

Infection of C57BL/6 mice with lymphocytic choriomeningitis virus (LCM V) stimulates major histocompatibility complex class I-restricted cyto toxic T cells (CTLs), which normally resolve the infection. Three pept ide epitopes derived from LCMV have been shown to bind the mouse class I molecule H-2 D-b and to stimulate CTL responses in LCMV-infected mi ce. This report describes the identity and abundance of each CTL epito pe after their elution from LCMV-infected cells. Based on this informa tion, peptide abundance was found to cell-elate with the magnitude of each CTL response generated after infection with LCMV. Subsequent expe riments, pet-formed to determine the antiviral capacity of each CTL sp ecificity, indicate that the quantitative hierarchy of CTL activity do es not con-elate with the ability to protect against LCMV infection. T his report, therefore, indicates that immunodominant epitopes should b e defined, not only by the strength of the CTL response that they stim ulate, but also by the ability of the CTLs to protect against infectio n.