Belonging to the CD1 family which plays non-redundant roles in lipid presentation, CD1c possesses the average binding pocket volume between CD1a and CD1b, but similar to CD1d. However, CD1c has proved to undergo conformational changes that can alter its binding pocket capacity, instrumental itself in accommodation of a wide range of lipids. Biologically, CD1c is one of the typical markers of dendritic and marginal zone B cells, yet the study on the role of CD1c in the immune system is limited in comparison with other CD1 isoforms until now. In the current study, we have discovered that CD1c can present two different lipids simultaneously. Especially, one of the two lipids, i.e. GD3 ganglioside, a regulator in cancer signalling, warps its massive headgroup around the distal F' portal of CD1c. The classical display position at the A' pocket is still occupied by either endogenous (monoacylglycerol, MAG) or exogenous (mycobacterial mannosyl phosphomycoketide, MPM) lipid. This finding indicates that CD1c can activate the T cell responses while the accommodated massive headgroup lipid does not block the autoreactive T cells toward the small lipid [1] or cytotoxic reactive T cells toward mycobacterial lipid [this study] in the A' pocket. Instead, CD1c may mediate the T-cell reactivity toward the massive headgroup lipid in an unconventional manner that is never seen before.