It is known that CD1 molecules can present a variety of glycolipids to natural killer T cells, but how differences in the lipid chains influence TCR recognition and why non-polymorphic CD1 molecules can accommodate extensive lipid diversity remain puzzling. In the Proceedings of the National Academy of Science, Garcia-Alles et al. provide hints by presenting the structure of human CD1b complexed with a sulfoglycolipid from Mycobacterium tuberculosis. They find that endogenous alkyldiacylglycerol lipids occupy lipid-binding grooves in the CD1b molecule, acting as 'spacers' or placeholders for exogenous lipids. Upon antigen loading, these spacers shift within the CD1b and lead to reorientation of A′ and F′ lipid-binding pockets. CD1b residues 149–152, located at the F′ pocket–TCR interface, shift by several angstroms and govern access to this pocket. These changes allow CD1b to bind bulky polar headgroups but limit the length of the alkyl chains that can be accommodated by the A′ pocket. This structural plasticity explains the ability of CD1b to present multiple glycolipids.

Proc. Natl. Acad. Sci. USA (17 October 2011) doi:10.1073/pnas.1110118108