Fine tuning by human CD1e of lipid-specific immune responses

Experimental Immunology, Department of Biomedicine, University Hospital Basel, 4031 Basel, Switzerland.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 08/2011; 108(34):14228-33. DOI: 10.1073/pnas.1108809108
Source: PubMed


CD1e is a member of the CD1 family that participates in lipid antigen presentation without interacting with the T-cell receptor. It binds lipids in lysosomes and facilitates processing of complex glycolipids, thus promoting editing of lipid antigens. We find that CD1e may positively or negatively affect lipid presentation by CD1b, CD1c, and CD1d. This effect is caused by the capacity of CD1e to facilitate rapid formation of CD1-lipid complexes, as shown for CD1d, and also to accelerate their turnover. Similar results were obtained with antigen-presenting cells from CD1e transgenic mice in which lipid complexes are assembled more efficiently and show faster turnover than in WT antigen-presenting cells. These effects maximize and temporally narrow CD1-restricted responses, as shown by reactivity to Sphingomonas paucimobilis-derived lipid antigens. CD1e is therefore an important modulator of both group 1 and group 2 CD1-restricted responses influencing the lipid antigen availability as well as the generation and persistence of CD1-lipid complexes.

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    • "In the presence of CD1e, PIM6 is cleaved to PIM2 and is loaded on CD1b (25). CD1e may also positively or negatively affect lipid presentation by CD1b, CD1c, and CD1d (73). This effect is achieved by a rapid formation of CD1–lipid complexes in the presence of CD1e, and also by an accelerated turnover of formed CD1–lipid antigen complexes. "
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    • "The hydrophobic amino acids surrounding the pockets facilitate anchoring of the aliphatic moieties of lipid antigens, thus protecting these from aqueous surrounding. CD1e molecules never reach cell surface and are involved in processing, loading and unloading of glycolipid antigens79. Therefore, CD1e is not a bona fide antigen-presenting molecule, however, it contributes to important aspects of lipid antigen presentation. "
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    • "This results in part from its capacity to accelerate the formation and dissociation of CD1-lipid complexes. Thus, CD1e participates in antigen presentation, not only by shaping the repertoire of available lipid antigens, but also by influencing the generation and persistence of group 1 and group 2 CD1-lipid complexes; i.e., it tunes T cell responses to CD1-restricted lipid antigens in a temporal manner [4]. "
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