Year: 2002
Type: article
Abstract: Most CD1d-dependent NKT cells in mice have a canonical V alpha 14J alpha 18 TCR rearrangement. However, relatively little is known concerning the molecular basis for their reactivity to glycolipid Ags presented by CD1d. Using glycolipid Ags, soluble forms of a V alpha 14 NKT cell-derived TCR, and mutant and wild-type CD1d molecules, we probed the TCR/CD1d interaction by surface plasmon resonance, tetramer equilibrium staining, and tetramer staining decay experiments. By these methods, several CD1d alpha-helical amino acids could be defined that do not greatly alter lipid binding, but that affect the interaction with the TCR. Binding of the V alpha 14(+) TCR to CD1d requires the agonist alpha-galactosylceramide (alpha-GalCer), as opposed to the nonantigenic beta-galactosylceramide, although both Ags bind to CD1d, indicating that the carbohydrate moiety of the CD1d-bound Ag plays a major role in the TCR interaction. The TCR has a relatively high-affinity binding to the alpha-GalCer/CD1d complex, with a particularly slow off rate. These unique properties are consistent with the coreceptor-independent action of the V alpha 14 TCR and may be related to the intense response to alpha-GalCer by NKT cells in vivo.
Source: The Journal of Immunology
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Awards: G1161347033, G1334773287, G1557902406, Selection of T-cell Receptor V-alpha Regions, Molecular Principles of TCR Recognition and Activation by peptide-MHC, ANTIGEN PRESENTATION AND IMMUNE REGULATION BY CD1, G5185286136, G549960583, Soluble T cell Receptor Studies on MHC Restriction, G6082723906, Protein Carbohydrate Interactions in Cell Communication, Recognition of bacterial antigens by NKT cells
OpenAlex ID: W2102016219