Table 2.

Some examples of major unanswered questions relating to type II NKT cells and their role in health and disease

• Is TCR recognition mechanism similar in murine and human type II NKT cells, including oligoclonality of the TCR   repertoire and whether other antigen-specific type II NKT cells use the similar TCR docking mechanism to that of sulfatide-   reactive NKT cells?

• Is there tissue specificity or bias in the cytokine secretion profiles or transcription factors involved in type II NKT cells   similar to that associated with Th1/Th2/Th17?

• What are the factors critical for the physiological activation of type II NKT cells in inflammatory conditions in both mice   and in humans?

• What are the conditions that favor type I versus type II NKT cell activation during disease and whether they can be   selectively targeted to control autoimmunity or to enhance anti-tumor immunity?

• Do alterations in Type II NKT cells correlate with disease pathology? Do changes in the level of underlying lipid antigen   lead to alteration in these cells in disease?

• Are microbial lipids recognized by human type II NKT cells? What are the functional consequences of recognition of self-   versus microbial lipids by human CD1d-restricted T cells? Is there TCR degeneracy or TCR promiscuity in recognition of   self vs. foreign lipids?

• Do all Type II NKT cells express NK markers?

• How self-lipids are transported in vivo to antigen-presenting cells and get presented?