Dr. Elizabeth Leadbetter's lab looks at the cooperation of NKT cells and B cells in response to lipid antigens.
Different from protein-reactive T cells, NK T cells are a unique cell population that recognizes lipids in the context of the CD1 family of antigen presenting molecules. Certain B cells recognize and internalize lipids and also express CD1 molecules on their surface, which makes them ideal partners for NK T cells.
Upon activation, NKT cells express co-stimulatory molecules and release cytokines which helps CD1d-expressing B cells to proliferate and increase their secretion of antibodies. Thus, NK T cells can improve a B cell’s response to antigens that they recognize in common.
They have already demonstrated that this cooperation happens using a model lipid conjugate. Future studies will investigate whether this same cooperation happens during the normal course of a bacterial infection and is important for defense against that infection.
They will also investigate the mechanism of this cooperation including the localization of these cells and their antigens in vivo.
Lipid-based vaccine strategies.
Another area of study in the lab includes testing vaccine candidates that couple the lipid component of our model antigen (the NKT cell-stimulating adjuvant) to unique B cell epitope-containing fragments from pathogens.
In this way, they will harness the ‘helper’ function of the NK T cells to activate and enhance the responses of B cells to otherwise weakly antigenic lipid or carbohydrate components of bacteria. It will be a universal approach that could apply to most types of bacteria, fungi, parasites, or other pathogens.
Lynch L, Michelet X, Zhang S, Brennan PJ, Moseman A, Lester C, Besra G,Vomhof-Dekrey EE, Tighe M, Koay HF, Godfrey DI, Leadbetter EA, Sant'Angelo DB, von Andrian U, Brenner MB. Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of T(reg) cells and macrophages in adipose tissue. Nat Immunol. 2015 Jan;16(1):85-95. doi:10.1038/ni.3047. Epub 2014 Dec 1.