Response to Listeria monocytogenes in mice lacking MHC class Ia molecules.
MHC class Ia-deficient mice (H2 Kb-/- Db-/-) inoculated with the intracellular pathogen Listeria monocytogenes (LM) displayed a three- to fourfold expansion of splenic CD8+ T cells 6 days following infection. Culture of these spleen cells in vitro gave rise to CTL that recognized LM-infected target cells and were restricted by the class Ib molecules, Qa1b and M3. Exposure 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 peptides known to bind M3, f-MIGWII, f-MIVTLF, and f-MIVIL, were recognized by effector cells from both B6 and Kb-/- Db-/- animals. In vivo analysis showed that B6 and Kb-/- Db-/- mice clear LM from the spleen and liver rapidly with similar kinetics, whereas TAP.1-/- mice, which are deficient in class Ia and Ib 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 protective immunity to syngeneic recipients. Spleen cells from Kb-/- Db-/- mice were also capable of generating responses directed against syngeneic as well as allogeneic class Ia molecules in vitro. Thus, class Ia-deficient animals have a CD8+ T cell repertoire capable of recognizing both class Ia and class Ib molecules and can generate protective immunity to LM.
Seaman
M S
MS
Immunology Graduate Program, Center for Immunology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Pérarnau
B
B
Lindahl
K F
KF
Lemonnier
F A
FA
Forman
J
J
D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D008089:Listeria monocytogenes / Q000276:immunology* / Q000472:pathogenicity; D008088:Listeriosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D008099:Liver / Q000382:microbiology; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D014774:Virulence
D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C024755:H-2K(K) antigen; C032876:H-2Kb protein, mouse; D015395:Histocompatibility Antigens Class I; C032907:Q surface antigens