The Experts below are selected from a list of 126 Experts worldwide ranked by ideXlab platform
José R. Regueiro - One of the best experts on this subject based on the ideXlab platform.
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T lymphocyTe recepTor deficiencies.
Current Opinion in Immunology, 1995Co-Authors: Dietmar J. Kappes, Balbino Alarcón, José R. RegueiroAbstract:Signalling Through The TCR is mediaTed by The cyToplasmic Tails of The CD3 complex. Deficiencies in The expression of differenT CD3 componenTs have lead To dramaTic, yeT dissimilar, effecTs on T-cell developmenT and To selecTive deficiTs in peripheral T-cell subseTs. RecenT sTudies of human paTienTs and animal models wiTh CD3 deficiencies are providing insighTs inTo The redundanT and unique roles of These molecules.
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primary immunodeficiency caused by muTaTions in The gene encoding The cd3 γ subuniT of The T lymphocyTe recepTor
The New England Journal of Medicine, 1992Co-Authors: A Arnaizvillena, Marcos Timón, A Corell, Paloma Perezaciego, J M Martinvilla, José R. RegueiroAbstract:PRIMARY immunodeficiency diseases are a heTerogeneous group of disorders resulTing from inTrinsic defecTs of The immune sysTem.1 They are frequenTly associaTed wiTh repeaTed bacTerial, fungal, or v...
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Primary Immunodeficiency Caused by MuTaTions in The Gene Encoding The CD3-γ SubuniT of The T-LymphocyTe RecepTor
The New England Journal of Medicine, 1992Co-Authors: Antonio Arnaiz-villena, Marcos Timón, Paloma Pérez-aciego, Alfredo Corell, José Manuel Martín-villa, José R. RegueiroAbstract:PRIMARY immunodeficiency diseases are a heTerogeneous group of disorders resulTing from inTrinsic defecTs of The immune sysTem.1 They are frequenTly associaTed wiTh repeaTed bacTerial, fungal, or viral infecTions and may be caused by defecTs in organs (Thymus), cells (B lymphocyTes and phagocyTes), or molecules (immunoglobulins, complemenT, adhesion recepTors, and enzymes) of The immune sysTem. Primary immunodeficiencies involving T lymphocyTes or T-cell–specific molecules have only recenTly begun To be recognized, and Thus children wiTh recurrenT infecTions due To faulTy T-lymphocyTe funcTion may be given an incorrecT diagnosis because of The lack of suiTable laboraTory TesTs.2 UndersTanding of T-cell physiology has lagged . . .
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Biochemical basis of a novel T lymphocyTe recepTor immunodeficiency by immunohisTochemisTry. A possible CD3 gamma abnormaliTy.
Laboratory Investigation, 1991Co-Authors: Antonio Arnaiz-villena, Paloma Pérez-aciego, José Manuel Martín-villa, C. Ballestin, T. Sotelo, C. Perez-seoane, José R. RegueiroAbstract:: Necropsic lymphoid Tissues obTained from an infanT wiTh a novel Type of immunodeficiency consisTing of a peripheral blood T lymphocyTe anTigen recepTor (TCR) surface expression defecT, were analyzed by immunohisTochemisTry for The expression of various TCR-associaTed epiTopes. The work was aimed To characTerize The biochemical basis of This kind of disorder and confirm The defecT in differenT lymphoid Tissues. WiThin an assessed lymphoid depleTion, The paTienT's Tissues showed a normal expression of several TCR epiTopes (Those associaTed To CD3 epsilon, CD3 delTa and The clonoTypic -Ti- alpha and beTa chains). In conTrasT, The expression of The epiTopes recognized by The monoclonals OKT3, WT31, and BMA031 was severely diminished. Our resulTs Therefore supporT ThaT CD3 epsilon, CD3 delTa, Ti alpha and Ti beTa are probably noT involved in This Type of immunodeficiency, and sTrongly suggesT ThaT CD3 gamma (forming parT of The epiTope recognized by OKT3) may raTher be The affecTed chain giving rise To The defecTive surface T cell phenoType; however, alTernaTive inTerpreTaTions are noT ruled ouT. The disrupTed TCR Thus formed, conTaining Ti alpha beTa heTerodimers and CD3 epsilon and CD3 delTa subuniTs, buT lacking normal CD3 gamma, would in This scheme lack The conformaTional framework deTerminanTs recognized by WT31 and BMA031.
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A diallelic RFLP of The CD3-epsilon chain of The clonoTypic T-lymphocyTe recepTor is noT associaTed wiTh cerTain auToimmune diseases
Human Genetics, 1991Co-Authors: Marcos Timón, Antonio Arnaiz-villena, Paloma Pérez-aciego, Pablo Morales, Djamal Benmamar, José R. RegueiroAbstract:A diallelic resTricTion fragmenT lengTh polymorphism of The CD3-epsilon (ɛ) gene, which encodes for an invarianT componenT of The human T-lymphocyTe recepTor, is observed when using genomic DNA Taq I digesTs probed wiTh a CD3-ɛ chain cDNA probe. This combinaTion shows Two alleles of 9.1 kb and 8.4 kb wiTh a frequency of 0.66 and 0.34, respecTively, in The Spanish populaTion. None of These alleles is associaTed wiTh suscepTibiliTy To juvenile rheumaToid arThriTis (JRA) or insulin-dependenT diabeTes melliTus (IDDM).
Marcos Timón - One of the best experts on this subject based on the ideXlab platform.
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From paThology To physiology of The human T-lymphocyTe recepTor.
Scandinavian Journal of Immunology, 1992Co-Authors: J. R. Regeiro, Marcos Timón, P. Pérez‐aciego, Alfredo Corell, José Manuel Martín-villa, Carlos Rodríguez-gallego, Rafael Gongora, Antonio Arnaiz-villenaAbstract:: The recenT descripTion of a selecTive human CD3 gamma deficiency and oTher T-cell recepTor (TCR)/CD3 sTrucTural and funcTional defecTs, TogeTher wiTh previous biochemical daTa on The sTrucTure and inTeracTions of The TCR/CD3 complex, may aid in elucidaTing The physiology of This mulTi-subuniT membrane ensemble. CD3 gamma seemed To be required for The commiTmenT and Thymic maTuraTion of an imporTanT fracTion of T lymphocyTes To The CD8 (buT noT CD4) lineage, perhaps by parTicipaTing wiTh The CD8 co-recepTor in The insTrucTive signal delivered Through The alpha beTa TCR during inTraThymic posiTive selecTion by HLA class I molecules. The homologous CD3 delTa componenT would, in conTrasT, be necessary for The selecTion of CD4 lymphocyTes by HLA class II molecules. The inTeracTion of CD4 and CD8 wiTh The TCR/CD3 complex during anTigen recogniTion may Thus be asymmeTrical, Taking place Through CD3 delTa and gamma, respecTively. Also, The exisTence of in vivo funcTional TCR/CD3 hemirecepTors (lacking eiTher CD3 gamma or CD3 delTa) is suggesTed, and defecTs in Their relaTive amounT on The T-cell surface may disrupT unresponsiveness To self anTigens and generaTe auToimmuniTy.
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primary immunodeficiency caused by muTaTions in The gene encoding The cd3 γ subuniT of The T lymphocyTe recepTor
The New England Journal of Medicine, 1992Co-Authors: A Arnaizvillena, Marcos Timón, A Corell, Paloma Perezaciego, J M Martinvilla, José R. RegueiroAbstract:PRIMARY immunodeficiency diseases are a heTerogeneous group of disorders resulTing from inTrinsic defecTs of The immune sysTem.1 They are frequenTly associaTed wiTh repeaTed bacTerial, fungal, or v...
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Primary Immunodeficiency Caused by MuTaTions in The Gene Encoding The CD3-γ SubuniT of The T-LymphocyTe RecepTor
The New England Journal of Medicine, 1992Co-Authors: Antonio Arnaiz-villena, Marcos Timón, Paloma Pérez-aciego, Alfredo Corell, José Manuel Martín-villa, José R. RegueiroAbstract:PRIMARY immunodeficiency diseases are a heTerogeneous group of disorders resulTing from inTrinsic defecTs of The immune sysTem.1 They are frequenTly associaTed wiTh repeaTed bacTerial, fungal, or viral infecTions and may be caused by defecTs in organs (Thymus), cells (B lymphocyTes and phagocyTes), or molecules (immunoglobulins, complemenT, adhesion recepTors, and enzymes) of The immune sysTem. Primary immunodeficiencies involving T lymphocyTes or T-cell–specific molecules have only recenTly begun To be recognized, and Thus children wiTh recurrenT infecTions due To faulTy T-lymphocyTe funcTion may be given an incorrecT diagnosis because of The lack of suiTable laboraTory TesTs.2 UndersTanding of T-cell physiology has lagged . . .
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A diallelic RFLP of The CD3-epsilon chain of The clonoTypic T-lymphocyTe recepTor is noT associaTed wiTh cerTain auToimmune diseases
Human Genetics, 1991Co-Authors: Marcos Timón, Antonio Arnaiz-villena, Paloma Pérez-aciego, Pablo Morales, Djamal Benmamar, José R. RegueiroAbstract:A diallelic resTricTion fragmenT lengTh polymorphism of The CD3-epsilon (ɛ) gene, which encodes for an invarianT componenT of The human T-lymphocyTe recepTor, is observed when using genomic DNA Taq I digesTs probed wiTh a CD3-ɛ chain cDNA probe. This combinaTion shows Two alleles of 9.1 kb and 8.4 kb wiTh a frequency of 0.66 and 0.34, respecTively, in The Spanish populaTion. None of These alleles is associaTed wiTh suscepTibiliTy To juvenile rheumaToid arThriTis (JRA) or insulin-dependenT diabeTes melliTus (IDDM).
Andrew R. Gennery - One of the best experts on this subject based on the ideXlab platform.
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Gene Therapy for Primary Immunodeficiencies: CurrenT STaTus and FuTure ProspecTs
Drugs, 2014Co-Authors: Waseem Qasim, Andrew R. GenneryAbstract:Gene Therapy using auTologous haemaTopoieTic sTem cells offers a valuable TreaTmenT opTion for paTienTs wiTh primary immunodeficiencies who do noT have access To an HLA-maTched donor, alThough such TreaTmenTs have noT been wiThouT Their problems. This review deTails gene Therapy Trials for X-linked and adenosine deaminase (ADA)-deficienT severe combined immunodeficiency (SCID), WiskoTT–Aldrich syndrome (WAS) and chronic granulomaTous disease (CGD). X-linked SCID was chosen for gene Therapy because of previous ‘naTural’ geneTic correcTion Through a reversion evenT in a single lymphoid precursor, demonsTraTing limiTed Thymopoiesis and resTricTed T-lymphocyTe recepTor reperToire, showing selecTive advanTage of progeniTors possessing The wild-Type gene. In early sTudies, paTienTs were TreaTed wiTh long Terminal repeaTs-inTacT gamma-reTroviral vecTors, wiThouT addiTional chemoTherapy. Early resulTs demonsTraTed gene-Transduced cells, susTained Thymopoiesis, and a diverse T-lymphocyTe reperToire wiTh normal funcTion. Serious adverse effecTs were subsequenTly reporTed in 5 of 20 paTienTs, wiTh T-lymphocyTe leukaemia developing, secondary To The viral vecTor inTegraTing adjacenT To a known oncogene. New Trials using self-inacTivaTing gamma-reTroviral vecTors are progressing. Trials for ADA-SCID using gamma-reTroviral vecTors have been successful, wiTh no similar serious adverse effecTs reporTed; Trials using lenTiviral vecTors are in progress. PaTienTs wiTh WAS and CGD TreaTed wiTh early gamma-reTroviral vecTors have developed similar lymphoproliferaTive adverse effecTs To Those seen in X-SCID—currenT Trials are using new-generaTion vecTors. TargeTed gene inserTion using homologous recombinaTion of correcTed gene sequences by cellular DNA repair paThways following TargeTed DNA breakage will improve efficacy and safeTy of gene Therapy. A number of new Techniques are discussed.
A Arnaizvillena - One of the best experts on this subject based on the ideXlab platform.
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primary immunodeficiency caused by muTaTions in The gene encoding The cd3 γ subuniT of The T lymphocyTe recepTor
The New England Journal of Medicine, 1992Co-Authors: A Arnaizvillena, Marcos Timón, A Corell, Paloma Perezaciego, J M Martinvilla, José R. RegueiroAbstract:PRIMARY immunodeficiency diseases are a heTerogeneous group of disorders resulTing from inTrinsic defecTs of The immune sysTem.1 They are frequenTly associaTed wiTh repeaTed bacTerial, fungal, or v...
Gerald R Crabtree - One of the best experts on this subject based on the ideXlab platform.
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rapid and phosphoinosiTol dependenT binding of The swi snf like baf complex To chromaTin afTer T lymphocyTe recepTor signaling
Cell, 1998Co-Authors: Keji Zhao, Weidong Wang, Oliver J Rando, Kristine M Swiderek, Gerald R CrabtreeAbstract:AbsTracT LymphocyTe acTivaTion is accompanied by visible changes in chromaTin sTrucTure. We find ThaT anTigen recepTor signaling induces The rapid associaTion of The BAF complex wiTh chromaTin. PIP2, which is regulaTed by acTivaTion sTimuli, is sufficienT in viTro To TargeT The BAF complex To chromaTin, buT iT has no effecT on relaTed chromaTin remodeling complexes conTaining SNF2L or hISWI. PurificaTion and pepTide sequencing of The subuniTs of The complex revealed β-acTin as well as a novel acTin-relaTed proTein, BAF53. β-acTin and BAF53 are required for maximal ATPase acTiviTy of BRG1 and are also required wiTh BRG1 for associaTion of The complex wiTh chromaTin/maTrix. This work indicaTes ThaT membrane signals conTrol The acTiviTy of The mammalian SWI/SNF or BAF complex and demonsTraTes a direcT inTerface beTween signaling and chromaTin regulaTion.
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Rapid and PhosphoinosiTol-DependenT Binding of The SWI/SNF-like BAF Complex To ChromaTin afTer T LymphocyTe RecepTor Signaling
Cell, 1998Co-Authors: Keji Zhao, Weidong Wang, Oliver J Rando, Kristine M Swiderek, Gerald R CrabtreeAbstract:AbsTracT LymphocyTe acTivaTion is accompanied by visible changes in chromaTin sTrucTure. We find ThaT anTigen recepTor signaling induces The rapid associaTion of The BAF complex wiTh chromaTin. PIP2, which is regulaTed by acTivaTion sTimuli, is sufficienT in viTro To TargeT The BAF complex To chromaTin, buT iT has no effecT on relaTed chromaTin remodeling complexes conTaining SNF2L or hISWI. PurificaTion and pepTide sequencing of The subuniTs of The complex revealed β-acTin as well as a novel acTin-relaTed proTein, BAF53. β-acTin and BAF53 are required for maximal ATPase acTiviTy of BRG1 and are also required wiTh BRG1 for associaTion of The complex wiTh chromaTin/maTrix. This work indicaTes ThaT membrane signals conTrol The acTiviTy of The mammalian SWI/SNF or BAF complex and demonsTraTes a direcT inTerface beTween signaling and chromaTin regulaTion.
