CD1 antigen presentation: how it works

Barral, Duarte C.; Brenner, Michael B.

doi:10.1038/nri2191

Cited by 304 publications

(330 citation statements)

References 133 publications

Supporting

Mentioning

325

Contrasting

Unclassified

Order By: Relevance

“…NK cell cytolytic activity is also induced through the expression of cell stress-induced MHC class I-related chain A (MICA) and B (MICB) proteins (10). In contrast, CD8 + T cells kill target cells by recognition of MHC-I restricted peptide antigens or CD1-restricted nonpeptide antigens (11,12). For the recognition of antigens, CD8 + T cells use an antigen-specific receptor, which is the outcome of genomic segment recombination during the development (13).…”

Section: Introductionmentioning

confidence: 99%

Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

et al. 2009

View full text Add to dashboard Cite

One of the functions of the immune system is to recognize and destroy abnormal or infected cells to maintain homeostasis. This is accomplished by cytotoxic lymphocytes. Cytotoxicity is a highly organized multifactor process. Here, we reviewed the apoptosis pathways induced by the two main cytotoxic lymphocyte subsets, natural killer (NK) cells and CD8 + T cells. In base to recent experimental evidence, we reviewed NK receptors involved in recognition of target-cell, as well as lytic molecules such as perforin, granzymes-A and -B, and granulysin. In addition, we reviewed the Fas-FasL intercellular linkage mediated pathway, and briefly the cross-linking of tumor necrosis factor (TNF) and TNF receptor pathway. We discussed three models of possible molecular interaction between lytic molecules from effector cytotoxic cells and target-cell membrane to induction of apoptosis. Cellular & Molecular Immunology. 2009;6(1):15-25.

show abstract

Section: Introductionmentioning

confidence: 99%

Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

et al. 2009

View full text Add to dashboard Cite

show abstract

“…The trafficking routes of CD1b, CD1c and CD1d are different from that of CD1a, since all these molecules reach LE and Ly, whereas CD1a traffics only through EE (reviewed in [44]). CD1b is internalized through clathrin-coated pits after binding of the adaptor protein AP2 to its cytoplasmic domain.…”

Section: Trafficking Of Cd1 Molecules and Antigen Loading In Differenmentioning

confidence: 99%

“…CD1a forms supercomplexes with MHC class II molecules and the invariant chain and traffics to the plasma membrane where it localizes within detergent-resistant membrane regions together with CD9 [42]. CD1a is internalized through a clathrin-and dynamin-independent, and Rab22a-and ARF6-dependent route into EE and recycles through sorting endosomes, without reaching LE [43].The trafficking routes of CD1b, CD1c and CD1d are different from that of CD1a, since all these molecules reach LE and Ly, whereas CD1a traffics only through EE (reviewed in [44]). CD1b is internalized through clathrin-coated pits after binding of the adaptor protein AP2 to its cytoplasmic domain.…”

mentioning

confidence: 99%

The cellular and biochemical rules of lipid antigen presentation

2009

View full text Add to dashboard Cite

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...

show abstract

“…The CD1 family is a group of non-polymorphic glycoproteins that present lipid antigens to T cells (Porcelli & Modlin 1999;Brigl & Brenner 2004;Barral & Brenner 2007). Like MHC class I proteins, CD1 proteins are heterodimers of b2 microglobulin and a heavy chain consisting of three extracellular a domains, a transmembrane region and a cytoplasmic tail, each encoded by a separate exon, preceded by an exon that encodes the start codon and signal peptide, and sometimes an additional exon that consists of 5′ UTR only.…”

Section: Cd1 Dog Microsatellite Nkt Cells Simple Sequence Repeatmentioning

confidence: 99%

Tandem repeats modify the structure of the canine CD1D gene

et al. 2012

View full text Add to dashboard Cite

SummaryAmong the CD1 proteins that present lipid antigens to T cells, CD1d is the only one that stimulates a population of T cells with an invariant T-cell receptor known as NKT cells. Sequencing of a 722 nucleotide gap in the dog (Canis lupus familiaris) genome revealed that the canine CD1D gene lacks a sequence homologous to exon 2 of human CD1D, coding for the start codon and signal peptide. Also, the canine CD1D gene contains three different short tandem repeats that disrupt the expected gene structure. Because canine CD1D cDNA lacks sequences homologous to human exon 2 and 3, the functionality of canine CD1d protein may be affected, and this could have consequences for the development and activation of canine NKT cells. Keywords CD1, dog, microsatellite, NKT cells, simple sequence repeatThe CD1 family is a group of non-polymorphic glycoproteins that present lipid antigens to T cells (Porcelli & Modlin 1999;Brigl & Brenner 2004;Barral & Brenner 2007). Like MHC class I proteins, CD1 proteins are heterodimers of b2 microglobulin and a heavy chain consisting of three extracellular a domains, a transmembrane region and a cytoplasmic tail, each encoded by a separate exon, preceded by an exon that encodes the start codon and signal peptide, and sometimes an additional exon that consists of 5′ UTR only.Large variation exists in the number of CD1A, CD1B, and CD1C genes between mammalian species, whereas one or two CD1D genes are present in all mammalian species studied to date (Dascher et al. 1999;Hayes & Knight 2001;Eguchi-Ogawa et al. 2007;Looringh van Beeck et al. 2008. CD1d is crucial for the selection (Bendelac et al. 1995) and activation (Kawano et al. 1997) of a subset of T cells known as natural killer T (NKT) cells. The canine CD1 locus is located on chromosome 38 and contains one CD1D gene, eight CD1A genes, one CD1C, one CD1B and one CD1E gene (Fig. 1a) (Looringh van Beeck et al. 2008). In the canine genome (CanFam 3.1) and in the sequence of BAC clone XX-14K12 AC183576.27, the canine CD1D gene is incomplete due to an internal gap of unknown length. Upstream from this gap we detected a sequence with 62% nt identity to exon 1 of human CD1D and downstream from the gap a sequence with 68% identity to human exon 3 (ENST00000368171; www.ensembl.org) (Fig. 1b). No canine homolog of the human CD1D exon 2 was found. Putative full-length canine exons were found for CD1D exon 4, 5, 6 and 7, with identities of respectively 76%, 84%, 58% and 56% to the corresponding human exons.To be able to fill the gap in the genomic DNA sequence between exon 1 and exon 3 of canine CD1D, we performed a two-step digestion on BAC clone XX-14K12 DNA using restriction endonuclease HpaI followed by HindIII and NotI (Fig. S1). The two restriction fragments containing the gap were subsequently cloned and sequenced. The complete DNA sequence of the gap was obtained and consists of 722 nt (GenBank GU930707) (Fig. 1c). No canine homolog of the human CD1D exon 2 was found in this DNA sequence.Using Tandem Repeat Finder, three different types ...

show abstract

CD1 antigen presentation: how it works

Cited by 304 publications

References 133 publications

Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

The cellular and biochemical rules of lipid antigen presentation

Tandem repeats modify the structure of the canine CD1D gene

Contact Info

Product

Resources

About