Assistance of Microbial Glycolipid Antigen Processing by CD1e

Salle, Henri; Mariotti, Sabrina; Angénieux, Catherine; Gilleron, Martine; Garcia-Alles, Luis F.; Malm, Dag; Berg, Thomas; Paoletti, Samantha; Maître, Blandine; Mourey, Lionel; Salamero, Jean; Cazenave, J.‐P.; Hanau, Daniel; Mori, Lucia; Puzo, Germain; Libero, Gennaro De

doi:10.1126/science.1115301

Cited by 226 publications

(237 citation statements)

References 23 publications

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“…CD1e assists processing by the lysosomal α-mannosidase of mycobacterial hexamannosylated phosphatidyl-myoinositols (PIM 6 ), containing six α-D-Manp units, into dimannosylated forms (PIM 2 ), containing only two α-D-Manp units (4). This form of PIM is stimulatory to specific CD1b-restricted T cells.…”

Section: Cd1 Restriction | Lipid Transfer Proteins | Natural Killer Tmentioning

confidence: 99%

Fine tuning by human CD1e of lipid-specific immune responses

Facciotti

Cavallari

Angénieux

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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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.CD1 restriction | lipid transfer proteins | natural killer T cells

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Section: Cd1 Restriction | Lipid Transfer Proteins | Natural Killer Tmentioning

confidence: 99%

Fine tuning by human CD1e of lipid-specific immune responses

Facciotti

Cavallari

Angénieux

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Moreover, several studies have also shown that all M.tb PIMs interact with dendritic cellspecific ICAM-3-grabbing non-integrin (DC-SIGN) (Torrelles et al, 2006), although differences in DC-SIGN PIM recognition specificity may be species dependent . Additional studies have also shown that cytosolic soluble CD1e is involved in PIM 6 processing and presentation via CD1 with subsequent T cell activation (de la Salle et al, 2005) (Table 1).…”

Section: The Peripheral Lipid Layer In the M Tuberculosis Cell Wallmentioning

confidence: 99%

Broadening Our View About the Role of Mycobacterium tuberculosis Cell Envelope Components During Infection: A Battle for Survival

Torrelles¹

2012

Understanding Tuberculosis - Analyzing the Origin of Mycobacterium Tuberculosis Pathogenicity

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“…They include lipoarabinomannan (LAM) and lipomannan (LM) [3,4], phosphatidylinositol mannosides (PIM) [3,5], mycolic acid [6], glucose monomycolate [7], glycerol monomycolate [8] and diacylated sulphoglycolipids [9]. Mycolic acids are a family of a-branched, a-hydroxy fatty acids.…”

Section: Structure Of Exogenous and Self-lipid Antigensmentioning

confidence: 99%

“…Lipids with large hydrophilic moieties form antigenic complexes with CD1 molecules after partial degradation. The hydrolases a-galactosidase A, hexosaminidase B and acidic a-mannosidase are involved in partial degradation of glycolipid antigens [5,54,55], thus indicating that glycolipid processing takes advantage of different enzymes involved in lysosomal glycolipid degradation. Whether lipases contribute to lipid antigen processing is unknown.…”

Section: Lipid Antigen Processing and Loading On Cd1 Moleculesmentioning

confidence: 99%

“…Another LTP is CD1e that is present as soluble form in Ly of activated DC. CD1e is absolutely required for processing of complex mycobacterial antigens, such as PIM 6 [5], because it binds PIM 6 and facilitates its solubilization and digestion by lysosomal a-mannosidase into the antigenic PIM 2 . CD1e is the most polymorphic CD1 molecule (six alleles have been identified so far), with allele 4 characterized by inefficient assembly, poor transport to LE and altered immunological function [61].…”

Section: Lipid Antigen Processing and Loading On Cd1 Moleculesmentioning

confidence: 99%

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The cellular and biochemical rules of lipid antigen presentation

2009

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The recognition of both protein and lipid antigens follows similar strategies that rely on different molecular mechanisms. APC present lipid antigens exploiting the same mechanisms implicated in lipid translocation, lipoprotein assembly and lipid degradation. An important issue is how the lipid structure contributes to antigenicity. Lipid hydrophobicity influences the modes of internalization by APC, the trafficking through different membrane compartments, the binding to CD1 molecules and the stability of antigenic complexes. Some glycolipids with large hydrophilic parts require processing of the sugar moieties exerted by lysosomal hydrolases. Finally, extraction of lipids from membranes, their solubilization and loading on CD1 molecules are facilitated by the same lysosomal lipid-binding proteins that are also instrumental in lipid catabolism. More recent investigations reveal how lipid-specific immunity is regulated during infections. In this review we describe the main cellular and biochemical rules of lipid antigen presentation and discuss their implications in anti-microbial and autoimmune responses.Key words: Antigen recognition . CD1 . Lipid antigens . TCR IntroductionMembers of the MHC or CD1 families present protein and lipid antigens to T cells, respectively. CD1 molecules are differentially expressed by a variety of cell types including DC, B cells, monocytes, Langerhans cells, stellate hepatic cells, epithelial cells, microglial cells and keratinocytes. In humans, five genes (CD1A, B, C, D and E) encode CD1 proteins. CD1a, CD1b, CD1c and CD1d molecules reach the plasma membrane and are involved in lipid presentation to T cells, whereas CD1e remains intracellular and is involved in lipid processing. Lipid-specific T cells express a variety of TCR heterodimers, with the exception of invariant NKT (iNKT) cells, a CD1d-restricted population that uses a semi-invariant TCR (invariant Va24-Ja18 and variable Vb11 chains in humans, invariant Va14-Ja18 and variable Vb8.2, Vb7 or Vb2 chains in mice).Proteins become antigenic after a series of events starting with partial degradation by the cellular machinery represented by the proteasome or by proteases located in lysosomes (Ly) and endoplasmic reticulum (ER). This immunological function, commonly known as antigen processing, leads to the generation of peptide fragments that are carried to the proximity of MHC molecules with which they form antigenic complexes. A similar scheme applies to the presentation of lipid antigens. Lipids derived from extracellular routes are internalized or alternatively, self-lipid antigens are synthesized within the APC. These lipids are then transported into the cellular compartments where CD1 molecules traffic and after loading onto CD1, form antigenic complexes.The physicochemical properties of lipids and peptides impose the utilization of different strategies by the APC to digest, transport and load each of these classes of molecules. Antigenicity of lipids is achieved with the participation of extracellular and intracellular li...

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Assistance of Microbial Glycolipid Antigen Processing by CD1e

Cited by 226 publications

References 23 publications

Fine tuning by human CD1e of lipid-specific immune responses

Fine tuning by human CD1e of lipid-specific immune responses

Broadening Our View About the Role of Mycobacterium tuberculosis Cell Envelope Components During Infection: A Battle for Survival

The cellular and biochemical rules of lipid antigen presentation

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