The biology of NKT cells.
Recognized more than a decade ago, NKT cells differentiate from mainstream thymic precursors through instructive signals emanating during TCR engagement by CD1d-expressing cortical thymocytes. Their semi-invariant alphabeta TCRs recognize isoglobotrihexosylceramide, a mammalian glycosphingolipid, as well as microbial alpha-glycuronylceramides found in the cell wall of Gram-negative, lipopolysaccharide-negative bacteria. This dual recognition of self and microbial ligands underlies innate-like antimicrobial functions mediated by CD40L induction and massive Th1 and Th2 cytokine and chemokine release. Through reciprocal activation of NKT cells and dendritic cells, synthetic NKT ligands constitute promising new vaccine adjuvants. NKT cells also regulate a range of immunopathological conditions, but the mechanisms and the ligands involved remain unknown. NKT cell biology has emerged as a new field of research at the frontier between innate and adaptive immunity, providing a powerful model to study fundamental aspects of the cell and structural biology of glycolipid trafficking, processing, and recognition.
Bendelac
Albert
A
Howard Hughes Medical Institute, Committee on Immunology, Department of Pathology University of Chicago, Chicago, Illinois 60637, USA. abendela@bsd.uchicago.edu
Savage
Paul B
PB
Teyton
Luc
L
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D001324:Autoantigens / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology / Q000494:pharmacology; D023201:CD40 Ligand / Q000276:immunology; D018925:Chemokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005915:Globosides / Q000276:immunology; D005963:Glucosylceramides / Q000276:immunology; D006090:Gram-Negative Bacteria / Q000276:immunology; D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D018448:Models, Immunological; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014281:Trihexosylceramides / Q000276:immunology
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D018949:Antigens, CD1; D055610:Antigens, CD1d; D001324:Autoantigens; D001428:Bacterial Vaccines; C526877:CD1D protein, human; D018925:Chemokines; D005915:Globosides; D005963:Glucosylceramides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014281:Trihexosylceramides; C514781:isoglobotrihexosylceramide; D023201:CD40 Ligand