Glycosylphosphatidylinositol (GPI)-anchored surface antigens in the allogeneic activation of T cells

Schubert, Jörg; Stroehmann, A.; Scholz, Claudia; Schmidt, Reinhold

doi:10.1111/j.1365-2249.1995.tb06656.x

Cited by 13 publications

(1 citation statement)

References 25 publications

(18 reference statements)

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“…CD59, the principal ligand for CD2, has been shown to enhance T-cell activation and proliferation following cross-linking with CD2 [ 56 ]. Both these GPI-anchored markers were shown to be involved in proliferation of T-cells in patients suffering from bone marrow failure [ 57 ] and paroxysmal nocturnal haemoglobinuria [ 58 ]. The ability to regulate the activity and proliferative ability of T-cells through the control of GPI-anchor attachment suggest PERLD1's involvement in the inflammatory aspect of asthma.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study identifies PERLD1 as asthma candidate gene

et al. 2011

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BackgroundRecent genome-wide association studies (GWAS) for asthma have been successful in identifying novel associations which have been well replicated. The aim of this study is to identify the genetic variants that influence predisposition towards asthma in an ethnic Chinese population in Singapore using a GWAS approach.MethodsA two-stage GWAS was performed in case samples with allergic asthma, and in control samples without asthma and atopy. In the discovery stage, 490 case and 490 control samples were analysed by pooled genotyping. Significant associations from the first stage were evaluated in a replication cohort of 521 case and 524 control samples in the second stage. The same 980 samples used in the discovery phase were also individually genotyped for purposes of a combined analysis. An additional 1445 non-asthmatic atopic control samples were also genotyped.Results19 promising SNPs which passed our genome-wide P value threshold of 5.52 × 10-8 were individually genotyped. In the combined analysis of 1011 case and 1014 control samples, SNP rs2941504 in PERLD1 on chromosome 17q12 was found to be significantly associated with asthma at the genotypic level (P = 1.48 × 10-6, ORAG = 0.526 (0.369-0.700), ORAA = 0.480 (0.361-0.639)) and at the allelic level (P = 9.56 × 10-6, OR = 0.745 (0.654-0.848)). These findings were found to be replicated in 3 other asthma GWAS studies, thus validating our own results. Analysis against the atopy control samples suggested that the SNP was associated with allergic asthma and not to either the asthma or allergy components. Genotyping of additional SNPs in 100 kb flanking rs2941504 further confirmed that the association was indeed to PERLD1. PERLD1 is involved in the modification of the glycosylphosphatidylinositol anchors for cell surface markers such as CD48 and CD59 which are known to play multiple roles in T-cell activation and proliferation.ConclusionsThese findings reveal the association of a PERLD1 as a novel asthma candidate gene and reinforce the involvement of genes on the 17q12-21 chromosomal region in the etiology of asthma.

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Section: Discussionmentioning

confidence: 99%

Genome-wide association study identifies PERLD1 as asthma candidate gene

et al. 2011

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Rat T cells express neither CD55 nor CD59 and are dependent on Crry for protection from homologous complement

et al. 2002

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All human blood cells express decay‐accelerating factor (DAF, CD55), CD59, and, with the exception of erythrocytes, membrane cofactor protein (MCP, CD46) to protect themselves from damage by the constant low‐level activation of complement in serum. In rats and mice MCP is expressed only in testis, whereas DAF and CD59 are broadly distributed. Rats and mice also express a unique complement regulator, Crry. Previously we have shown that DAF was absent from at least 75% of rat T cells. To further investigate this surprising finding, we assessed the expression levels of DAF, CD59 and Crry on all blood cell types in the rat. We found that Crry was abundantly expressed on all blood cells. CD59 was expressed abundantly on erythrocytes and granulocytes but was absent from all T cellsand platelets and a minority of B cells and NK cells. Double staining and depletion studies showed that T cells in all rat strains tested were DAF– CD59–. Neutralization of Crry using a blocking monoclonal antibody rendered T cells susceptible to lysis by homologous complement, indicating that Crry was solely responsible for protecting DAF– CD59– T cells from complement damage in the rat.

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Glycosylphosphatidylinositol-linked proteins are required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development

et al. 2002

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Surface proteins tethered to the membrane through a glycosylphosphatidylinositol (GPI) anchor are deficient in the blood cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) as result of a somatic mutation, in a hematopoietic stem cell, of the X‐linked phosphatidylinositolglycan complementation group A (PIG‐A) gene. In PNH patients, compared to the large numbers of GPI‐deficient myeloid cells, the proportion of GPI‐deficient lymphocytes tends to be low, and therefore the impact of GPI deficiency on immune function has been unclear. We have obtained complementation by Pig‐a– embryonic stem (ES) cells of Rag–/– blastocysts, and we show that Pig‐a– ES cells are able to reconstitute the T cell and B cell compartments of Rag–/– mice. Although these mice were immunologically competent, by comparison with appropriate controls we detected several abnormalities: (1) increased levels of IgG; (2) high frequency/titers of anti‐nuclear antibodies; (3) markedly reduced delayed hypersensitivity; and (4) impaired activation‐induced lymphocyte death in vitro. In some cases, aging Pig‐a–/Rag–/– chimeric mice developed lymphadenopathy and polyclonal T cell and B cell expansion. Thus, GPI‐linked proteins are not required for lymphocyte development but they are required for normal lymphocyte function and for maintaining normal peripheral lymphoid homeostasis.

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Glycosylphosphatidylinositol (GPI)-anchored surface antigens in the allogeneic activation of T cells

Cited by 13 publications

References 25 publications

Genome-wide association study identifies PERLD1 as asthma candidate gene

Genome-wide association study identifies PERLD1 as asthma candidate gene

Rat T cells express neither CD55 nor CD59 and are dependent on Crry for protection from homologous complement

Glycosylphosphatidylinositol-linked proteins are required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development

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