Functional CD1a is stabilized by exogenous lipids.
Self-glycosphingolipids bind to surface CD1 molecules and are readily displaced by other CD1 ligands. This capacity to exchange antigens at the cell surface is not common to other antigen-presenting molecules and its physiological importance is unclear. Here we show that a large pool of cell-surface CD1a, but not CD1b molecules, is stabilized by exogenous lipids present in serum. Under serum deprivation CD1a molecules are altered and functionally inactive, as they are unable to present lipid antigens to T cells. Glycosphingolipids and phospholipids bind to, and restore functionality to CD1a without the contribution of newly synthesized and recycling CD1a molecules. The dependence of CD1a stability on exogenous lipids is not related to its intracellular traffic and rather to its antigen-binding pockets. These results indicate a functional dichotomy between CD1a and CD1b molecules and provide new information on how the lipid antigenic repertoire is immunologically sampled.
Manolova
Vania
V
Experimental Immunology, Department of Research University Hospital, Basel, Switzerland.
Kistowska
Magdalena
M
Paoletti
Samantha
S
Baltariu
Gabriel M
GM
Bausinger
Huguette
H
Hanau
Daniel
D
Mori
Lucia
L
De Libero
Gennaro
G
D018949:Antigens, CD1 / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006028:Glycosphingolipids / Q000494:pharmacology; D006801:Humans; D007801:Langerhans Cells / Q000737:chemistry; D008055:Lipids / Q000494:pharmacology*; D018613:Microscopy, Confocal; D010743:Phospholipids / Q000494:pharmacology; D017510:Protein Folding; D044967:Serum / Q000502:physiology; D013433:Sulfoglycosphingolipids / Q000494:pharmacology; D001613:beta 2-Microglobulin / Q000494:pharmacology
D018949:Antigens, CD1; C419393:CD1a antigen; D006028:Glycosphingolipids; D008055:Lipids; D010743:Phospholipids; D013433:Sulfoglycosphingolipids; D001613:beta 2-Microglobulin