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The Journal of Immunology, 2000, 164: 5005-5009.
Copyright © 2000 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: The IgG Response to the Circumsporozoite Protein Is MHC Class II-Dependent and CD1d-Independent: Exploring the Role of GPIs in NK T Cell Activation and Antimalarial Responses1

Alberto Molano*, Se-Ho Park{dagger}, Ya-Hui Chiu{dagger}, Sandy Nosseir*, Albert Bendelac{dagger} and Moriya Tsuji2,*

* Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010; and {dagger} Department of Molecular Biology, Princeton University, Princeton, NJ 08544

Biochemical analysis has suggested that self GPI anchors are the main natural ligand associated with mouse CD1d molecules. A recent study reported that V{alpha}14+ NK T cells responded to self as well as foreign (parasite-derived) GPIs in a CD1d-dependent manner. It further reported that the IgG response to the Plasmodium berghei malarial circumsporozoite (CS) protein was severely impaired in CD1d-deficient mice, leading to a model whereby NK T cells, upon recognition of CD1d molecules presenting the CS-derived GPI anchor, provide help for B cells secreting anti-CS Abs. We tested this model by comparing the anti-CS Ab responses of wild-type, CD1d-deficient, and MHC class II-deficient mice. We found that the IgG response to the CS protein was solely MHC class II-dependent. Furthermore, by measuring the response of a broad panel of CD1d-autoreactive T cells to GPI-deficient CD1d-expressing cells, we found that GPIs were not required for autoreactive responses.




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