Immunity to blood-stage murine malarial parasites is MHC class II dependent.
To determine whether MHC class II antigen presentation is essential for the induction of protective immunity against blood-stage malarial parasites, we used gene-targeted knockout (KO) mice to follow the time-course of nonlethal Plasmodium yoelii and Plasmodium chabaudi infections in two models of MHC class II deficiency. Infection of MHC class II KO (A(-/-)) mice with either parasite species resulted in an unremitting hyperparasitemia, whereas MHC-intact control mice resolved their parasitemia. In contrast, invariant chain KO (Ii(-/-)) mice, which present antigen via recycled but not nascent MHC class II molecules, eventually cured their infections when infected with P. yoelii. P. chabaudi parasitemia declined to subpatent levels in most Ii(-/-) mice but then recrudesced. Immunity to blood-stage malaria may be achieved by cell-mediated and antibody-mediated mechanisms of immunity, as such, the findings in A(-/-) mice indicate an essential role for MHC class II presentation of malarial antigens. Moreover, they suggest that protective immune responses to malarial antigens capable of eliminating blood-stage parasites are T cell dependent and can be induced with antigens processed in early and late endosomes.
Cigel
Francine
F
Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, 1300 University Avenue, Madison, WI 53706, USA.
Batchelder
Joan
J
Burns
James M
JM
Yañez
Deborah
D
van der Heyde
Henri
H
Manning
Dean D
DD
Weidanz
William P
WP
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D008288:Malaria / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016788:Plasmodium chabaudi / Q000276:immunology*; D010967:Plasmodium yoelii / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000949:Histocompatibility Antigens Class II