Glycolipid activators of invariant NKT cells as vaccine adjuvants

Natural Killer T cells (NKT cells) are a subpopulation of T lymphocytes with unique phenotypic properties and a remarkably broad range of immune effector and regulatory functions. One subset of these cells, known as invariant NKT cells (iNKT cells), has become a significant focus in the search for new and better ways to enhance immunotherapies and vaccination. These unconventional T cells are characterized by their ability to be specifically activated by a range of foreign and self-derived glycolipid antigens presented by CD1d, an MHC class I-related antigen presenting molecule that has evolved to bind and present lipid antigens. The development of synthetic α-galactosylceramides as a family of powerful glycolipid agonists for iNKT cells has led to approaches for augmenting a wide variety of immune responses, including those involved in vaccination against infections and cancers. Here we review the basic background biology of iNKT cells that is relevant to their potential for improving immune responses, and summarize recent work supporting the further development of glycolipid activators of iNKT cells as a new class of vaccine adjuvants.