Costimulation via CD55 on Human CD4+ T Cells Mediated by CD97

Capasso, Melania; Durrant, Lindy G.; Stacey, Martin; Gordon, Siamon; Ramage, Judith M.; Spendlove, Ian

doi:10.4049/jimmunol.177.2.1070

Cited by 93 publications

(101 citation statements)

References 40 publications

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“…The two molecules shared almost identical EGF-like domains and 50% homology in the stalk and the 7TM regions. As well as functional roles in leukocyte migration, recruitment and activation [18][19][20][21], CD97 is known to be involved in angiogenesis and the migration and invasion of tumor cells [22][23][24]. By analyzing the GPS cleavage of CD97-mFc-fusion protein, we show herein that CD97 and EMR2 have very different GPS cleavage efficiencies.…”

Section: Introductionmentioning

confidence: 84%

Site‐specific N‐glycosylation regulates the GPS auto‐proteolysis of CD97

et al. 2009

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a b s t r a c tAuto-proteolysis at the G protein-coupled receptor (GPCR) proteolytic site (GPS) is a hallmark of adhesion-GPCRs. Although defects in GPS auto-proteolysis have been linked to genetic disorders, information on its regulation remains elusive. Here, we investigated the GPS proteolysis of CD97, a human leukocyte-restricted and tumor-associated adhesion-GPCR. We found that CD97 is incompletely processed, unlike its close homolog, epidermal growth factor-like module-containing mucin-like hormone receptor 2. A unique pattern of N-glycosylation within the GPS motif of related adhesion-GPCRs was identified. The use of N-glycosylation inhibitors and mutants confirm site-specific N-glycosylation is an important determinant of GPS proteolysis in CD97. Our results suggest that N-glycosylation may regulate the processing of adhesion-GPCRs leading to the production of either cleaved or uncleaved molecules.

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Section: Introductionmentioning

confidence: 84%

Site‐specific N‐glycosylation regulates the GPS auto‐proteolysis of CD97

et al. 2009

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“…Both molecules are early activation antigens and are induced on T lymphocytes by the engagement of T-cell receptor/CD3 complex [20]. Indeed, there were few naïve T cells expressing CD25 and CD69 on the surface (less than 2% cells, data not shown).…”

Section: Lps Activates Cd8 1 T Cells and Induces Perforin And Granzymmentioning

confidence: 90%

“…To further analyse the activating role of LPS on CD8 1 T cells, the purified CD8 1 T cells were cultured with either anti-CD3 with or without LPS or IL-12 in the presence or absence of LPS for 72 h. The activation markers, CD25, the IL-2 receptor a-chain and CD69 (a phosphorylated homodimeric surface protein) were detected by FACS [20]. (Fig.…”

Section: Lps Activates Cd8 1 T Cells and Induces Perforin And Granzymmentioning

confidence: 99%

Direct recognition of LPS by human but not murine CD8⁺ T cells via TLR4 complex

Komai-Koma¹,

Gilchrist²,

Xu³

2009

Eur J Immunol

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LPS comprises a major PAMP and is a key target of the immune system during bacterial infection. While LPS can be recognised by innate immune cells via the TLR4 complex, it is unknown whether T lymphocytes, especially CD8 1 T cells are also capable of doing so. We report here that naïve human CD8 1 T cells, after activation by TCR stimulation, express surface TLR4 and CD14. These activated CD8 1 T cells can then secrete high concentrations of IFN-c, granzyme and perforin in response to LPS. These effects can be specifically inhibited using siRNA for TLR4. Furthermore, LPS can synergise with IL-12 to polarise the CD8 1 T cells into cytotoxic T-cell 1 (Tc1) that produce IFN-c but not IL-4, with or without TCR activation. Moreover, CD8 1 CD45RO 1 memory T cells constitutively expressed TLR4 and markedly enhanced IFN-c production when stimulated with LPS. In contrast, activated murine CD8 1 T cells lack TLR4 and CD14 expression and fail to respond to LPS for proliferation and cytokine production. Thus, human but not murine CD8 1 T cells are able to directly recognise bacterial LPS via LPS receptor complex and TLR4 provides a novel signal for the activation of effector and memory human CD8 1 T cells.Key words: CD14 . CD8 1 T cells . Tc1 . LPS . TLR Supporting Information available online IntroductionLPS is an abundant glycolipid in the outer-membrane of Gramnegative bacteria [1][2][3]. It consists of hydrophobic lipid A, the o-polysaccharide chain and a core oligosaccharide [3][4][5]. LPS is perhaps the most well-studied microbial molecule due to its powerful immune activating properties, extremely stable nature and wide distribution in the environment [1][2][3]. It is the key molecule responsible for the bacteria-triggered inflammatory response resulting in organ failure and death [1][2][3]. LPS is also closely associated with pathogenesis of many inflammatory diseases [1][2][3][4]. Despite this, the proinflammatory effects of LPS when harnessed may be beneficial; its powerful effect on both innate and adaptive immunity may provide a new generation of immune adjuvants for vaccine development against infection and cancer [2-4]. Therefore, a clearer understanding of how host recognises LPS is fundamentally important.TLR are a group of evolutionarily developed pathogen-pattern recognition receptors that are widely distributed on immune cells [3,5]. At least ten members of the TLR family in humans have been identified. These recognise different microbial products from bacteria, virus, fungi and parasites [2][3][4]. Host cells recognise LPS via a receptor complex consisting of TLR4, CD14 and MD2 in which LPS only signals through TLR4 and triggers cellular activation and expression of inflammatory genes [2][3][4]. Since TLR was originally identified in Drosophila, which lacks an adaptive immune system, the initial belief was that recognition of pathogen products was a characteristic of innate cells bearing 1564TLR [5,6]. However, the role of T cells bearing TLR in pathogen recognition is less well understood.Growing evide...

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“…DAF, in addition to those roles seen previously in suppressing T-cell responses in vivo, may also play a role in costimulation. It has been reported that the coengagement of DAF and CD3 results in the proliferation of CD4 T cells, indicating that the role DAF plays in T-cell biology is, at best, multifaceted [139].…”

Section: Complement System In Adaptive Immunity: T-cell Immunitymentioning

confidence: 99%

Complement and its role in innate and adaptive immune responses

2009

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The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.

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Costimulation via CD55 on Human CD4+ T Cells Mediated by CD97

Cited by 93 publications

References 40 publications

Site‐specific N‐glycosylation regulates the GPS auto‐proteolysis of CD97

Site‐specific N‐glycosylation regulates the GPS auto‐proteolysis of CD97

Direct recognition of LPS by human but not murine CD8⁺ T cells via TLR4 complex

Complement and its role in innate and adaptive immune responses

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Costimulation via CD55 on Human CD4+ T Cells Mediated by CD97

Cited by 93 publications

References 40 publications

Site‐specific N‐glycosylation regulates the GPS auto‐proteolysis of CD97

Site‐specific N‐glycosylation regulates the GPS auto‐proteolysis of CD97

Direct recognition of LPS by human but not murine CD8+ T cells via TLR4 complex

Complement and its role in innate and adaptive immune responses

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Direct recognition of LPS by human but not murine CD8⁺ T cells via TLR4 complex