Response to Listeria monocytogenes in mice lacking MHC class Ia molecules

MHC class Ia-deficient mice (H2 Kb-/- Db-/-) inoculated with the intracellu lar pathogen Listeria monocytogenes (LM) displayed a three- to fourfold exp ansion of splenic CD8(+) T cells 6 days following infection. Culture of the se spleen cells in vitro gave rise to CTL that recognized LM-infected targe t cells and were restricted by the class Ib molecules, Qa1(b) and M3, Expos ure of target cells to heat-killed LM (HKLM) rather than live bacteria did not result in CTL-mediated lysis. Target cells pulsed with three LM peptide s known to bind M3, f-MIGWII, f-MITVTLF, and f-MIVIL, were recognized by ef fector cells from both B6 and Kb-/- animals. In vivo analysis showed that B 6 and Kb-/- Db-/- mice clear LM from the spleen and liver rapidly with simi lar kinetics, whereas TAP.1(-/-) mice, which are deficient in class Ia and rb molecules, clear LM slowly upon infection, To establish the in vivo role of CD8(+) T cells in Kb-/- Db-/- animals, we showed that depletion of such cells from the spleens of immune mice prevented the adoptive transfer of p rotective immunity to syngeneic recipients. Spleen cells from Kb-/- Db-/- m ice were also capable of generating responses directed against syngeneic as well as allogeneic class Ia molecules in vitro. Thus, class Ia-deficient a nimals have a CD8(+) T cell repertoire capable of recognizing both class Ia and class Ib molecules and can generate protective immunity to LM.