The Language Function Analysis 2011 Corpus (LFA-11) is a German text corpus of promotional text, reviews and blog posts on music and smartphones. The texts were manually classified with respect to their topic relevance, language function, and sentiment polarity.

LFA-1 (CD11a-CD18) - BioCentury Target Profiles for the biopharma industry

The role of Gαi proteins coupled to chemokine receptors in directed migration of immune cells is well understood. In this study we show that the separate class of Gαq/11 proteins is required for the underlying ability of T cells to migrate both randomly and in a directed chemokine-dependent manner. Interfering with Gαq or Gα11 using dominant negative cDNA constructs or siRNA for Gαq causes accumulation of LFA-1 adhesions and stalled migration. Gαq/11 has an impact on LFA-1 expression at plasma membrane level and also on its internalization. Additionally Gαq co-localizes with LFA-1- and EEA1-expressing intracellular vesicles and partially with Rap1- but not Rab11-expressing vesicles. However the influence of Gαq is not confined to the vesicles that express it, as its reduction alters intracellular trafficking of other vesicles involved in recycling. In summary vesicle-associated Gαq/11 is required for the turnover of LFA-1 adhesion that is necessary for migration. These G proteins participate directly in the initial phase of recycling and this has an impact on later stages of the endo-exocytic pathway.

This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp

The main entity of this document is a structure with accession number 1cqp

The integrin LFA-1 (CD11a/CD18) plays a critical role in the interaction of T cells with antigen presenting cells (APCs) to promote lymphocyte differentiation and proliferation. This integrin can be present either in a closed or in an open active conformation and its activation upon T-cell receptor (TCR) stimulation is a critical step to allow interaction with APCs. In this study we demonstrate that the serine/threonine kinase Ndr2 is critically involved in the initiation of TCR-mediated LFA-1 activation (open conformation) in T cells. Ndr2 itself becomes activated upon TCR stimulation and phosphorylates the intracellular integrin binding partner Filamin A (FLNa) at serine 2152. This phosphorylation promotes the dissociation of FLNa from LFA-1, allowing for a subsequent association of Talin and Kindlin-3 which both stabilize the open conformation of LFA-1. Our data suggest that Ndr2 activation is a crucial step to initiate TCR-mediated LFA-1 activation in T cells.

Protein-Protein, Genetic, and Chemical Interactions for Bechard D (2001):Human endothelial-cell specific molecule-1 binds directly to the integrin CD11a/CD18 (LFA-1) and blocks binding to intercellular adhesion molecule-1. curated by BioGRID (https://thebiogrid.org); ABSTRACT: ICAMs are ligands for LFA-1, a major integrin of mononuclear cells involved in the immune and inflammatory processes. We previously showed that endothelial cell specific molecule-1 (ESM-1) is a proteoglycan secreted by endothelial cells under the control of inflammatory cytokines. Here, we demonstrate that ESM-1 binds directly to LFA-1 onto the cell surface of human blood lymphocytes, monocytes, and Jurkat cells. The binding of ESM-1 was equally dependent on Ca(2+), Mg(2+), or Mn(2+) divalent ions, which are specific, saturable, and sensitive to temperature. An anti-CD11a mAb or PMA induced a transient increase in binding, peaking 5 min after activation. Direct binding of ESM-1 to LFA-1 integrin was demonstrated by specific coimmunoprecipitation by CD11a and CD18 mAbs. A cell-free system using a Biacore biosensor confirmed that ESM-1 and LFA-1 dynamically interacted in real time with high affinity (K(d) = 18.7 nM). ESM-1 consistently inhibited the specific binding of soluble ICAM-1 to Jurkat cells in a dose-dependent manner. These results suggest that ESM-1 and ICAM-1 interact with LFA-1 on binding sites very close to but distinct from the I domain of CD11a. Through this mechanism, ESM-1 could be implicated in the regulation of the LFA-1/ICAM-1 pathway and may therefore influence both the recruitment of circulating lymphocytes to inflammatory sites and LFA-1-dependent leukocyte adhesion and activation.

JAM-A plays a key role in leukocyte transmigration and inflammatory extravasation. Transmigration of human leukocytes has been shown to involve heterophilic interactions of JAM-A with its integrin receptor LFA-1.

integrin subunit alpha L Predicted to act upstream of or within cell adhesion. Predicted to be located in membrane. Predicted to be part of integrin complex. Orthologous to human ITGAL (integrin subunit alpha L).

Evidence-based product rating derived from 1 peer-reviewed scientific citations

IntroductionMortality from advanced HIV disease (AHD) remains high and current strategies to promptly test people eligible for AHD screening, are insufficient. Task sharing for point of care (POC) testing utilizing lay health workers (LHW) is recommended, however it is marginally practised in many countries. This study sought to describe the feasibility and testing outcomes of task-shared implementation of the AHD POC diagnostic tests utilizing LHW and professional health care workers (HCW).MethodsThis was a cross-sectional mixed-methods implementation study in seven primary and three secondary health facilities, in Mozambique and Democratic Republic of Congo (DRC). From March to November 2022, consenting HIV positive adults eligible for AHD screening, were offered Visitect CD4 lateral flow assay (LFA), and or subsequently urinary Mycobacterium tuberculosis lipoarabinomannan antigen (TB LAM) and cryptococcal antigen (CrAg) tests. The primary study outcome was the proportion of testers (LHW and HCW) who found it ‘easy’ to integrate the 3 POC tests within their routine work together with their opinions on the value of task shared AHD POC testing.ResultsA total of 1542 patients were screened for AHD by 35 LHW (34 counsellors, and 1 lay educator) and 45 professional HCW (28 nurses and 9 clinical officers and 8 doctors). In the study period, LHW conducted a median number of 27 [IQR: 16–34] Visitect CD4 LFA tests, whereas nurses, clinical officers together with doctors conducted 19 and 11 respectively. Visitect CD4 LFA increased CD4 testing by 10.7% in Munhava (Beira) and 22.9% in CHK (DRC), complementing existing CD4 testing instruments. Among testers who completed the feasibility survey, nearly sixty percent of testers (25/42; LHW in particular) found it easy to integrate AHD POC testing within their routine workflow.The prevalence of AHD was 39.2% (604/1542). A total of 34% (146/430) and 5.4% (22/407) of patients tested positive for urine TB LAM and plasma CrAg respectively. Of these, 82.2% (120/146) and 36.4% (8/22) had a documented therapeutic intervention. The median time for completing the Visitect CD4 LFA and conveying the results to the clinician was 59 minutes [IQR: 48–71].ConclusionTask-shared integrated testing for AHD at POC among LHW and professional HCW, is feasible and can improve access to AHD testing. However, as POC testing responsibilities become shared, documentation of testing activities could increase in complexity and can be easily fragmented, especially when there is limited supervision. Nevertheless, LHW are well suited for POC testing due to limited availability and higher clinical workload of other HCW.

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Protein-Protein, Genetic, and Chemical Interactions for Fujii T (2007):Roles played by lymphocyte function-associated antigen-1 in the regulation of lymphocytic cholinergic activity. curated by BioGRID (https://thebiogrid.org); ABSTRACT: Lymphocytes possess the essential components of a cholinergic system, including acetylcholine (ACh); choline acetyltransferase (ChAT), its synthesizing enzyme; and both muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively). Stimulation of lymphocytes with phytohemagglutinin, which activates T cells via the T cell receptor/CD3 complex, enhances the synthesis and release of ACh and up-regulates expression of ChAT and M(5) mAChR mRNAs. In addition, activation of protein kinase C and increases in intracellular cAMP also enhance cholinergic activity in T cells, and lymphocyte function associated antigen-1 (LFA-1; CD11a/CD18) is an important mediator of leukocyte migration and T cell activation. Anti-CD11a monoclonal antibody (mAb) as well as antithymocyte globulin containing antibodies against CD2, CD7 and CD11a all increase ChAT activity, ACh synthesis and release, and expression of ChAT and M(5) mAChR mRNAs in T cells. The cholesterol-lowering drug simvastatin inhibits LFA-1 signaling by binding to an allosteric site on CD11a (LFA-1 alpha chain), which leads to immunomodulation. We found that simvastatin abolishes anti-CD11a mAb-induced increases in lymphocytic cholinergic activity in a manner independent of its cholesterol-lowering activity. Collectively then, these results indicate that LFA-1 contributes to the regulation of lymphocytic cholinergic activity via CD11a-mediated pathways and suggest that simvastatin exerts its immunosuppressive effects in part via modification of lymphocytic cholinergic activity.

CD2 molecule Enables signaling receptor binding activity. Involved in several processes, including natural killer cell activation; natural killer cell mediated cytotoxicity; and positive regulation of cytokine production. Located in external side of plasma membrane. The protein encoded by this gene is a surface antigen found on all peripheral blood T-cells. The encoded protein interacts with LFA3 (CD58) on antigen presenting cells to optimize immune recognition. A locus control region (LCR) has been found in the 3' flanking sequence of this gene. [provided by RefSeq, Jun 2016]

Protein-Protein, Genetic, and Chemical Interactions for Kallen J (1999):Structural basis for LFA-1 inhibition upon lovastatin binding to the CD11a I-domain. curated by BioGRID (https://thebiogrid.org); ABSTRACT: The lymphocyte function-associated antigen (LFA-1) belongs to the family of beta2-integrins and plays an important role in T-cell activation and leukocyte migration to sites of inflammation. We report here that lovastatin, a drug clinically used for lowering cholesterol levels, inhibits the interaction of human LFA-1 with its counter-receptor intercellular adhesion molecule-1. Using nuclear magnetic resonance spectroscopy and X-ray crystallography we show that the inhibitor binds to a highly conserved domain of the LFA-1 alpha-chain called the I-domain. The first three-dimensional structure of an integrin inhibitor bound to its receptor reveals atomic details for a hitherto unknown mode of LFA-1 inhibition. It also sheds light into possible mechanisms of LFA-1 mediated signalling and will support the design of novel anti-adhesive and immunosuppressive drugs.

Patients screened for AHD per health facility tier level in all study sites.

Evidence-based product rating derived from 1 peer-reviewed scientific citations

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LFA Co Lagerdauer: 44,11 (2026). Historical annual data from 2006 to 2026 with forecasts.

Cd2 molecule Enables identical protein binding activity and receptor tyrosine kinase binding activity. Involved in cell-cell adhesion. Located in cell surface and plasma membrane. Part of protein-containing complex. Orthologous to human CD2 (CD2 molecule). Enables identical protein binding activity and receptor tyrosine kinase binding activity. Involved in cell-cell adhesion. Located in cell surface. Part of protein-containing complex. Orthologous to human CD2 (CD2 molecule); INTERACTS WITH 2,3,7,8-tetrachlorodibenzodioxine; acetamide; alpha-Zearalanol.