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 responses.
Biochemical analysis has suggested that self GPI anchors are the main natural ligand associated with mouse CD1d molecules. A recent study reported that Valpha14+ 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.
Molano
A
A
Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010, USA.
Park
S H
SH
Chiu
Y H
YH
Nosseir
S
S
Bendelac
A
A
Tsuji
M
M
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D018949:Antigens, CD1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010962:Plasmodium berghei / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D000913:Antibodies, Protozoan; D018949:Antigens, CD1; D017261:Glycosylphosphatidylinositols; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C041595:circumsporozoite protein, Protozoan