Partially TAP-independent protection against Listeria monocytogenes by H2-M3-restricted CD8+ T cells

Effective protection against Listeria monocytogenes requires Ag-specific CD8(+) T cells. A substantial proportion of CD8(+) T cells activated during L. monocytogenes infection of C57BL/6 mice are restricted by the MHC class Ib molecule H2-M3. In this study, an H2-M3-restricted CD8(+) T cell clone specific for a known H2-M3 epitope (fMIGWII) was generated from L. monocytogenes-infected mice. The clone was cytotoxic, produced IFN-gamma, and could mediate strong protection against L. monocytogenes when transferred to infected mice. Macrophages pulsed with heat-killed LISTERIAE: presented Ag to the clone in a TAP-independent manner. Both TAP-independent and -dependent processing occurred in vivo, as TAP-deficient mice infected with L. monocytogenes were partially protected by adoptive transfer of the clone. This is the first example of CD8(+) T cell-mediated, TAP-independent protection against a pathogen in vivo, confirming the importance of alternative MHC class I processing pathways in the antibacterial immunity.