Figure 3.

Antigenic changes during inflammation. (a) Altered lipid biosynthesis in myeloid APCs in response to TLR stimuli. Exposure of myeloid APCs to a variety of different TLR ligands appears to cause alterations in endogenous glycolipid biosynthesis. This may result in the de novo presentation of self antigens that are not normally expressed. Recent results suggest that TCR-mediated activation of NKT cells is enhanced as a result of the alterations in self lipid biosynthesis. References: ^120,121. (b) Recognition of a self lipid that becomes specifically up-regulated during inflammation. Upon encountering a variety of danger signals, myeloid APCs rapidly activate phospholipase A₂ enzymes. This results in increased cleavage of membrane phosphatidylcholine molecules, releasing free fatty acids that are used for eicosanoid (i.e. leukotriene, prostaglandin and lipoxin) biosynthesis. The other product from this reaction is lyso-phosphatidylcholine (LPC), which is able to be bound and presented by CD1d molecules. A fraction of human NKT cells have been found to recognize LPC as an antigen. Thus, the increased levels of LPC produced during inflammation may promote increased NKT cell activation. References: ^128–130.