TY - JOUR
T1 - Response to Listeria monocytogenes in mice lacking MHC class Ia molecules
AU - Seaman, Michael S.
AU - Pérarnau, Béatrice
AU - Fischer Lindahl, Kirsten
AU - Lemonnier, Francois A.
AU - Forman, James
PY - 1999/5/1
Y1 - 1999/5/1
N2 - MHC class Ia-deficient mice (H2 K(b-/-) D(b-/-)) 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 K(b-/-) D(b-/-) animals. In vivo analysis showed that B6 and K(b-/-) D(b-/-) 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 K(b-/-) D(b-/-) 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 K(b-/-) D(b-/-) 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.
AB - MHC class Ia-deficient mice (H2 K(b-/-) D(b-/-)) 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 K(b-/-) D(b-/-) animals. In vivo analysis showed that B6 and K(b-/-) D(b-/-) 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 K(b-/-) D(b-/-) 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 K(b-/-) D(b-/-) 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.
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M3 - Article
C2 - 10228021
AN - SCOPUS:0344655667
SN - 0022-1767
VL - 162
SP - 5429
EP - 5436
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -