CD4-INDEPENDENT IN-VIVO PRIMING OF MURINE CTL BY OPTIMAL MHC CLASS I-RESTRICTED PEPTIDES DERIVED FROM INTRACELLULAR PATHOGENS

CTL combat intracellular pathogens by killing infected cells. The mole cular targets of their attack are foreign peptides bound to self MHC e ncoded class I molecules. Immunization of mice with peptides containin g CTL determinants was shown to elicit CD4-dependent CTL. Here, we hav e achieved in vivo CTL priming with naturally processed 8-10 amino aci d long class I-restricted peptides emulsified in an adjuvant. A potent , reproducible and physiologically relevant response was obtained usin g peptides from an intracellular bacterium and five Viruses (including HIV) in two murine MHC haplotypes. This method is suitable for multip le vaccination, since a 'cocktail' of peptides derived from three path ogens elicited effector CTL against each pathogen. Most importantly, p eptide-induced CD8(+)CD4(-) CTL were CD4(+)-independent. These results have implications for CTL induction in situations where CD4 T cells a re depleted or compromised, as is the case in HIV infection.