The CD1d-binding glycolipid alpha-galactosylceramide enhances humoral immunity to T-dependent and T-independent antigen in a CD1d-dependent manner.
Specific interaction of class II/peptide with the T-cell receptor (TCR) expressed by class II-restricted CD4+ T helper (Th) cells is essential for in vivo production of antibodies reactive with T-dependent antigen. In response to stimulation with CD1d-binding glycolipid, Valpha14+ TCR-expressing, CD1d-restricted natural killer T (NKT) cells may provide additional help for antibody production. We tested the hypothesis that the CD1d-binding glycolipid alpha-galactosylceramide (alpha-GC) enhances production of antibodies reactive with T-dependent antigen in vivo. alpha-GC enhanced antibody production in vivo in a CD1d-dependent manner in the presence of class II-restricted Th cells and induced a limited antibody response in Th-deficient mice. alpha-GC also led to alterations in isotype switch, selectively increasing production of immunoglobulin G2b. Further analysis revealed that alpha-GC led to priming of class II-restricted Th cells in vivo. Additionally, we observed that alpha-GC enhanced production of antibodies reactive with T-independent antigen, showing the effects of NKT cells on B cells independently of Th cells. Our data show that NKT cells have multiple effects on the induction of a humoral immune response. We propose that NKT cells could be exploited for the development of novel vaccines where protective antibody is required.
Lang
Gillian A
GA
Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03766, USA.
Exley
Mark A
MA
Lang
Mark L
ML
D000818:Animals; D000917:Antibody Formation; D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013194:Staining and Labeling; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D018949:Antigens, CD1; D055610:Antigens, CD1d; D005699:Galactosylceramides; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D016693:Receptors, Antigen, T-Cell, alpha-beta; C493154:alpha-galactosylceramide; D010047:Ovalbumin