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Immune and Structural Studies of Synthetic Invariant Natural Killer T cell Glycosphingolipid Activators

  • Author(s): Birkholz, Alysia Marie
  • et al.
Abstract

Invariant Natural Killer T (iNKT) cells comprise a small fraction of immune cells capable of responding within hours when stimulated by glycosphingolipid (GSL) antigens (Ags) and can impact the immune system months later. These iNKT cells respond to GSLs that are presented by the antigen presenting molecule CD1d. The iNKT cell driven immune cytokine response can alter depending on the GSL that is presented by CD1d. The GSL can lead to the production of a T helper type 1 (Th1) or a T helper type 2 (Th2) response characterized by IFN-gamma and IL-4 cytokines. Many synthetic GSL analogs of the most common iNKT cell antigen, alpha-Galactosylceramide (aGalCer) were used in this study to determine immunological and biochemical properties of Ags capable of activating iNKT cells. Studies consisted of in vitro Ag binding models, crystallographic structural models and in vivo immunological studies. Ags that are categorized as Th1 iNKT cell cytokine skewers have properties correlated with this response. The Th1 Ags studied are presented by CD1d on dendritic antigen presenting cells (APCs) and the CD1d and GSL seem to form more contacts according to structural studies and the CD1d-GSL complexes are more biologically stable in vivo. The work from these studies adds the to growing information in the field regarding the nature of iNKT cell immune system skewing

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