Effects of Lipid Chain Lengths in α-Galactosylceramides on Cytokine Release by Natural Killer T Cells

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Abstract
Glycolipid presentation by CD1 proteins has emerged as an important aspect of antigen recognition, and presentation of α-glycosylceramides by CD1d to natural killer T cells has become a central focus in understanding how glycolipid presentation can influence immune responses. An α-galactosylceramide containing relatively long lipid chains has been the subject of intense study because, when presented by CD1d to natural killer T cells, it stimulates the release of both proinflammatory and immunomodulatory cytokines. Using an efficient synthesis of α-galactosylceramides, we have prepared a series of glycolipids in which the lipid chain lengths have been incrementally varied. The responses of natural killer T cells to these glycolipids have been determined, and we have found that truncation of the phytosphingosine lipid chain increases the relative amounts of immunomodulatory cytokines released. In similar fashion, the length of the acyl chain in α-galactosylceramides influences cytokine release profiles.