Abstract
AbstractOften referred to as the “Swiss Army knife” of the immune system, invariant natural killer T (iNKT) cells are a subpopulation of T lymphocytes stimulated by the synthetic glycolipid α‐galactosylceramide (αGalCer) when in complex with the CD1d receptor of antigen presenting cells. Through their ability to produce TH1 and TH2 cytokines and co‐stimulate several other lymphocytes, iNKT cells have emerged as central players in directing the immune response in a range of physiological processes, such as infections, autoimmune diseases, and cancer. Over the years, synthetic chemistry has advanced the field of iNKT cell stimulation with the development of more efficient approaches to prepare αGalCer, and, additionally, with the chemical synthesis of αGalCer analogs in the search of better TH1/TH2 cytokine skewing compounds for therapeutic applications. Here, we review the strategies for the synthesis of αGalCer and its analogs, including synthetic probes, together with the most important advances in the understanding of the mechanism of action of these compounds, as a guide to the available tools for interrogating the iNKT cell−αGalCer−CD1d complex and inspiration for future research.
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