DOCSLIB.ORG

Acquisition of CD80 (B7-1) by T Cells

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Acquisition of CD80 (B7-1) by T Cells Acquisition of CD80 (B7-1) by T Cells Helen Sabzevari,* Judy Kantor,* Adnan Jaigirdar,* Yutaka Tagaya,† Mayumi Naramura,‡ James W. Hodge,* John Bernon,* and Jeffrey Schlom1* Activation of T cells usually requires two signals. Signal 1 is mediated via a peptide-MHC on the APC; signal 2 is mediated via a costimulatory molecule on the APC surface. We demonstrate here that naive CD4؉ T cells actually acquire the costimulatory molecule CD80 (B7-1) from syngeneic APCs after activation. This phenomenon was demonstrated showing acquisition of CD80 by T cells from CD80/CD86 (B7-2) knockout mice, and by treating T cells with cyclohexamide to further rule out endogenous expression of CD80 by T cells. Moreover, no CD80 mRNA could be detected in T cells that had acquired CD80. The amount of acquisition of CD80 by T cells was shown to be directly related to both the strength of signal 1 and the amount of CD80 on the APC. Specificity of this acquisition was also shown by the lack of acquisition by T cells from CD28 knockout mice (implicating CD28 in this process), the lack of acquisition of CD40 (another molecule on the APC surface) by T cells, and confocal microscopy studies. We demonstrate for the first time that 1) naive T cells, following acquisition of CD80 from APCs, were themselves shown to be capable of acting as APCs; and 2) memory T cells that have acquired CD80 from APCs undergo apoptosis in the presence of increased levels of signal 1. Thus we demonstrate both immunostimulatory and immunoregulatory functions as a result of CD80 acquisition by different T cell populations. The Journal of Immunology, 2001, 166: 2505–2513. cell activation usually requires at least two different sig- reported increased levels of CD80 expression on both CD4ϩ and nals: 1) an Ag-specific signal (signal 1); and 2) a second, CD8ϩ cells in HIV-infected patients and revealed that these T cells T or costimulatory, signal (signal 2) that is provided by re- with accessory cell properties can costimulate proliferation in pu- ceptor ligand interaction between T cells and APCs, such as den- rified responder T cells from healthy control donors. Further stud- dritic cells (DCs).2 Although a variety of molecules reportedly ies of lupus patients have demonstrated that these individuals have have costimulation function, the majority of studies to date have increased amounts of CD80 on PBLs, including T cells (14). How- been focused on costimulation delivered via CD28 and CD80 in- ever, although all of these studies reported increased levels of teractions (1, 2). CD80 is a member of the Ig gene superfamily and CD80 molecules on T cells, none of the studies have actually dem- is expressed mainly on professional APCs; its receptor, CD28, is onstrated an endogenous up-regulation of CD80 molecules on T constitutively expressed on thymocytes and on most resting and cells (6–14). activated T cells. CD80 has also been shown to react with CTLA-4 In parallel murine studies, the amount of CD80 on T cells was on the surface of activated T cells; however, CTLA-4 has been reported to vary with the state of activation. Resting T cells dis- shown not to be expressed on resting T cells (3, 4). Interaction played little or no CD80; however, upon activation, CD80 levels of CD28 and CD80 prevents the induction of clonal anergy and on the cell surface increased concomitantly, peaking at 72 h (15). apoptosis of T cells (5). In a recent study, Weintraub et al. (16, 17) demonstrated that al- Various studies have reported that CD80 can also be detected on though splenic T cells from normal B6 mice were negative for activated human T cell clones, T cells activated repeatedly in vitro, CD80, freshly isolated T lymphocytes from the spleens of auto- and T cells that have infiltrated skin lesions and are in rheumatoid immune B6/gld and B6/lpr mice showed higher levels of CD80. synovial fluid (6–11). Studies by Kochli et al. that analyzed the This phenomenon was age dependent and may have contributed to expression of CD80 and MHC complex class II molecules on cir- lymphoproliferation and autoimmunity. Although these studies culating T cells of HIV-infected individuals have suggested that mentioned “increases in CD80 expression in T cells,” no data were these T cells develop an Ag-presenting phenotype by up-regulating actually presented in these studies as to whether these increases expression of HLA and CD80 (12). Moreover, Wolthers et al. (13) were due to up-regulation of CD80 in T cells or acquisition of CD80. *Laboratory of Tumor Immunology and Biology, Division of Basic Sciences, Na- Previous studies have demonstrated that T cells and thymocytes tional Cancer Institute; †Metabolism Branch, Division of Clinical Sciences, National can acquire MHC class I and class II determinants from other cells Cancer Institute; and ‡Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 present in the local environment (18, 19). Furthermore, it has been demonstrated that double-negative thymocytes can passively ac- Received for publication August 24, 2000. Accepted for publication December ϩ ϩ 4, 2000. quire a CD4 /CD8 determinant from other cells in the thymus ϩ ϩ The costs of publication of this article were defrayed in part by the payment of page that are actively expressing their CD4 /CD8 genes (20). A re- charges. This article must therefore be hereby marked advertisement in accordance cent study by Huang et al. (19) demonstrated that when peptide- with 18 U.S.C. Section 1734 solely to indicate this fact. specific T cells interacted with APCs, MHC molecules on APCs 1 Address correspondence and reprint requests to Dr. Jeffrey Schlom, Laboratory of formed clusters at the site of T cell contact. Afterward, these clus- Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 8B09, Bethesda, MD 20892-1402. E- ters were acquired by T cells and internalized through TCR endo- mail address: [email protected] cytosis. These studies also showed that the presence of APC-de- 2 Abbreviations used in this paper: DC, dendritic cell; KO, knockout; B7dKO, CD80/ rived peptide-MHC molecules on the T cell surface could make CD86 double-knockout; PCC/TCR-Tg, TCR transgenic for pigeon cytochrome c88–104; rF-CD80, recombinant fowlpox virus expressing CD80; FP-WT, wild-type fowlpox; these T cells susceptible to lysis by neighboring T cells. Moreover, GFP, green fluorescence protein; CHX, cyclohexamide. it has been reported recently that the activation of T cells with Copyright © 2001 by The American Association of Immunologists 0022-1767/01/$02.00 2506 ACQUISITION OF CD80 BY T CELLS Drosophila cells as APCs may result in the rapid transfer of MHC cells) and cultured with 1 ϫ 106 effector/memory T cells. The APCs were molecules and other costimulatory molecules, such as CD80, from separated from T cells 24 h later by a magnet. This procedure yielded a APCs to T cells (21). preparation of T cells devoid of any APCs. Although the concept of molecule acquisition by T cells origi- nated 20 years ago, the actual interactions of receptor ligands and Recombinant fowlpox viruses and infection of DCs the factors affecting ligand acquisition still remain unclear. In this Recombinant fowlpox virus expressing CD80 (rF-CD80) and wild-type regard, we analyzed CD80 levels on murine T cells upon stimu- fowlpox (FP-WT) have been described previously (24). DCs were har- lation with various APCs expressing different levels of CD80 on vested on day 6 of culture and washed with OptiMem (Life Technologies, Gaithersburg, MD). The cells (1.2 ϫ 106/ml) were infected with FP-WT or their surface. Although CD80 was previously thought to be endo- rF-CD80 at 50 MOI (multiplicity of infection; PFU/cells) for2hat37°C. genously up-regulated, results of studies of CD80/CD86 double- Cells were first washed and then incubated in condition medium at 37°C knockout (B7dKO) mice reported here demonstrate that CD80 is overnight. After 18 h, DCs were harvested for in vitro assays. physically acquired by T cells from APCs shortly after T cell ac- tivation. We also demonstrate here that CD80 acquisition by T Peptide cells is mediated by the TCR and its CD28 ligand (confirming the The I-Ek-restricted PCC peptide was synthesized and HPLC-purified by recent data by Hwang et al. (21)) and that the level of CD80 ac- American Peptide (Sunnyvale, CA). quisition by T cells is related to both the level of CD80 expression Cell preparation and culture on APCs and the strength of signal 1. Moreover, our data for the first time suggest that acquisition of CD80 by T cells might be of CD4ϩ cells were purified using microbeads conjugated to anti-CD4 mAb, importance for the Ag-presenting capacity of T cells. Thus, these according to the manufacturer’s instructions (MiniMACS, Miltenyi Bio- tec), on MACS columns. Isolated CD4ϩ cells (5 ϫ 105 cells/ml) were findings might have important implications for a further under- cultured with APCs (1 ϫ 105 cells/ml) with or without signal 1, with either standing of immune regulation and the pathogenesis of immuno- anti-CD3 Ab or PCC peptide (at concentrations indicated in each figure pathological diseases. legend), in RPMI 1640 supplemented with the following: 10% heat-inac- Ϫ5 tivated FBS, 5 ϫ 10 M 2-ME, 2 mM L-glutamine, 100 U/ml penicillin, Materials and Methods 100 ␮M/ml streptomycin, and 10 mM HEPES (all obtained from Life Technologies, Gaithersburg, MD), and 15 ␮g/ml gentamicin (BioWhit- Animals taker, Walkersville, MD).
Load more

Recommended publications
  • Costimulation of T-Cell Activation and Virus Production by B7 Antigen on Activated CD4+ T Cells from Human Immunodeficiency Virus Type 1-Infected Donors OMAR K
    Proc. Natl. Acad. Sci. USA Vol. 90, pp. 11094-11098, December 1993 Immunology Costimulation of T-cell activation and virus production by B7 antigen on activated CD4+ T cells from human immunodeficiency virus type 1-infected donors OMAR K. HAFFAR, MOLLY D. SMITHGALL, JEFFREY BRADSHAW, BILL BRADY, NITIN K. DAMLE*, AND PETER S. LINSLEY Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121 Communicated by Leon E. Rosenberg, August 3, 1993 (receivedfor review April 29, 1993) ABSTRACT Infection with the human immunodeficiency sequence (CTLA-4) (34), a protein structurally related to virus type 1 (HIV-1) requires T-cefl activation. Recent studies CD28 but only expressed on T cells after activation (12). have shown that interactions of the T-lymphocyte receptors CTLA-4 acts cooperatively with CD28 to bind B7 and deliver CD28 and CTLA-4 with their counter receptor, B7, on antigen- T-cell costimulatory signals (13). presenting cells are required for optimal T-cell activation. Here Because of the importance of the CD28/CTLA-4 and B7 we show that HIV-1 infection is associated with decreased interactions in immune responses, it is likely that these expression of CD28 and increased expression of B7 on CD4+ interactions are also important during HIV-1 infection. Stud- T-cell lines generated from seropositive donors by afloantigen ies with anti-CD28 monoclonal antibodies (mAbs) suggested stimulation. Loss of CD28 expression was not seen on CD4+ a role for CD28 in up-regulating HIV-1 long terminal repeat- T-ceU lines from seronegative donors, but up-regulation of B7 driven transcription of a reporter gene in leukemic cell lines expression was observed upon more prolonged culture.
    [Show full text]
  • Inhibition of Midkine Alleviates Experimental Autoimmune Encephalomyelitis Through the Expansion of Regulatory T Cell Population
    Inhibition of midkine alleviates experimental autoimmune encephalomyelitis through the expansion of regulatory T cell population Jinyan Wang*, Hideyuki Takeuchi*†, Yoshifumi Sonobe*, Shijie Jin*, Tetsuya Mizuno*, Shin Miyakawa‡, Masatoshi Fujiwara‡, Yoshikazu Nakamura§¶, Takuma Katoʈ, Hisako Muramatsu**, Takashi Muramatsu**††, and Akio Suzumura*† *Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; ‡RIBOMIC, Inc., 3-15-5-601 Shirokanedai, Minato-ku, Tokyo 108-0071, Japan; §Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; ¶Core Research Evolutional Science and Technology, Japan Science and Technology Agency, Toyonaka, Osaka 560-8531, Japan; ʈDepartment of Bioregulation, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan; **Department of Biochemistry, Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; and ††Department of Health Science, Faculty of Psychological and Physical Sciences, Aichi Gakuin University, Nisshin, Aichi 470-0195, Japan Edited by Ethan Shevach, National Institutes of Health, Bethesda, MD, and accepted by the Editorial Board January 20, 2008 (received for review October 12, 2007) CD4؉CD25؉ regulatory T (Treg) cells are crucial mediators of nity, and abnormalities in Treg cell function may contribute to the autoimmune tolerance. The factors that regulate Treg cells, how- development of
    [Show full text]
  • Immunomodulation and Generation of Tolerogenic Dendritic Cells by Probiotic Bacteria in Patients with Inflammatory Bowel Disease
    International Journal of Molecular Sciences Article Immunomodulation and Generation of Tolerogenic Dendritic Cells by Probiotic Bacteria in Patients with Inflammatory Bowel Disease 1, 2, 1 Shaghayegh Baradaran Ghavami y, Abbas Yadegar y , Hamid Asadzadeh Aghdaei , Dario Sorrentino 3,4,*, Maryam Farmani 1 , Adil Shamim Mir 5, Masoumeh Azimirad 2 , Hedieh Balaii 6, Shabnam Shahrokh 6 and Mohammad Reza Zali 6 1 Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; [email protected] (S.B.G.); [email protected] (H.A.A.); [email protected] (M.F.) 2 Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; [email protected] (A.Y.); [email protected] (M.A.) 3 IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, USA 4 Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, 33100 Udine, Italy 5 Department of Internal Medicine, Roanoke Memorial Hospital, Carilion Clinic, VA 24014, USA; [email protected] 6 Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; [email protected] (H.B.); [email protected] (S.S.); [email protected] (M.R.Z.) * Correspondence: [email protected] These authors equally contributed to this study. y Received: 7 August 2020; Accepted: 27 August 2020; Published: 29 August 2020 Abstract: In inflammatory bowel diseases (IBD), the therapeutic benefit and mucosal healing from specific probiotics may relate to the modulation of dendritic cells (DCs).
    [Show full text]
  • Galectin-4 Interaction with CD14 Triggers the Differentiation of Monocytes Into Macrophage-Like Cells Via the MAPK Signaling Pathway
    Immune Netw. 2019 Jun;19(3):e17 https://doi.org/10.4110/in.2019.19.e17 pISSN 1598-2629·eISSN 2092-6685 Original Article Galectin-4 Interaction with CD14 Triggers the Differentiation of Monocytes into Macrophage-like Cells via the MAPK Signaling Pathway So-Hee Hong 1,2,3,4,5, Jun-Seop Shin 1,2,3,5, Hyunwoo Chung 1,2,4,5, Chung-Gyu Park 1,2,3,4,5,* 1Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul 03080, Korea 2Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 03080, Korea 3Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea 4Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea 5Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, Korea Received: Jan 28, 2019 ABSTRACT Revised: May 13, 2019 Accepted: May 19, 2019 Galectin-4 (Gal-4) is a β-galactoside-binding protein mostly expressed in the gastrointestinal *Correspondence to tract of animals. Although intensive functional studies have been done for other galectin Chung-Gyu Park isoforms, the immunoregulatory function of Gal-4 still remains ambiguous. Here, we Department of Microbiology and Immunology, Seoul National University College of Medicine, demonstrated that Gal-4 could bind to CD14 on monocytes and induce their differentiation 103 Daehak-ro, Jongno-gu, Seoul 03080, into macrophage-like cells through the MAPK signaling pathway. Gal-4 induced the phenotypic Korea. changes on monocytes by altering the expression of various surface molecules, and induced E-mail: [email protected] functional changes such as increased cytokine production and matrix metalloproteinase expression and reduced phagocytic capacity.
    [Show full text]
  • Antibody to CD40 Ligand Inhibits Both Humoral and Cellular Immune Responses to Adenoviral Vectors and Facilitates Repeated Administration to Mouse Airway
    Gene Therapy (1997) 4, 611–617 1997 Stockton Press All rights reserved 0969-7128/97 $12.00 Antibody to CD40 ligand inhibits both humoral and cellular immune responses to adenoviral vectors and facilitates repeated administration to mouse airway A Scaria1, JA St George1, RJ Gregory1, RJ Noelle2, SC Wadsworth1, AE Smith1 and JM Kaplan1 1Genzyme Corporation, Framingham, MA; 2Department of Microbiology, Dartmouth Medical School, Lebanon, NH, USA Adenoviral vectors have been used successfully to transfer against murine CD40 ligand inhibits the development of the human CFTR cDNA to respiratory epithelium in animal neutralizing antibodies to adenoviral (Ad) vector. MR1 also models and to CF patients in vivo. However, studies done decreased the cellular immune response to Ad vector and primarily in mice, indicate that present vector systems have allowed an increase in persistence of transgene limitations. Among other things, transgene expression in expression. Furthermore, when administered with a the lung is transient and the production of neutralizing anti- second dose of Ad vector to mice preimmunized against bodies against adenovirus correlates with a reduced ability vector, MR1 was able to interfere with the development of to readminister a vector of the same serotype. Here we a secondary antibody response and allowed for high levels demonstrate that in mice, a transient blockade of costimu- of transgene expression upon a third administration of lation between activated T cells and B cells/antigen vector to the airway. presenting cells
    [Show full text]
  • B Cell Checkpoints in Autoimmune Rheumatic Diseases
    REVIEWS B cell checkpoints in autoimmune rheumatic diseases Samuel J. S. Rubin1,2,3, Michelle S. Bloom1,2,3 and William H. Robinson1,2,3* Abstract | B cells have important functions in the pathogenesis of autoimmune diseases, including autoimmune rheumatic diseases. In addition to producing autoantibodies, B cells contribute to autoimmunity by serving as professional antigen- presenting cells (APCs), producing cytokines, and through additional mechanisms. B cell activation and effector functions are regulated by immune checkpoints, including both activating and inhibitory checkpoint receptors that contribute to the regulation of B cell tolerance, activation, antigen presentation, T cell help, class switching, antibody production and cytokine production. The various activating checkpoint receptors include B cell activating receptors that engage with cognate receptors on T cells or other cells, as well as Toll-like receptors that can provide dual stimulation to B cells via co- engagement with the B cell receptor. Furthermore, various inhibitory checkpoint receptors, including B cell inhibitory receptors, have important functions in regulating B cell development, activation and effector functions. Therapeutically targeting B cell checkpoints represents a promising strategy for the treatment of a variety of autoimmune rheumatic diseases. Antibody- dependent B cells are multifunctional lymphocytes that contribute that serve as precursors to and thereby give rise to acti- cell- mediated cytotoxicity to the pathogenesis of autoimmune diseases
    [Show full text]
  • Inflammatory Lesions (CD80) and B7.2 (CD86) in Vitro and In
    Human Muscle Cells Express a Functional Costimulatory Molecule Distinct from B7.1 (CD80) and B7.2 (CD86) In Vitro and in Inflammatory Lesions This information is current as of September 26, 2021. Lüder Behrens, Martin Kerschensteiner, Thomas Misgeld, Norbert Goebels, Hartmut Wekerle and Reinhard Hohlfeld J Immunol 1998; 161:5943-5951; ; http://www.jimmunol.org/content/161/11/5943 Downloaded from References This article cites 49 articles, 19 of which you can access for free at: http://www.jimmunol.org/content/161/11/5943.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 26, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 1998 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Human Muscle Cells Express a Functional Costimulatory Molecule Distinct from B7.1 (CD80) and B7.2 (CD86) In Vitro and in Inflammatory Lesions1 Lu¨der Behrens,* Martin Kerschensteiner,* Thomas Misgeld,* Norbert Goebels,*† Hartmut Wekerle,* and Reinhard Hohlfeld2*† The B7 family of costimulatory molecules likely includes members distinct from B7.1 (CD80) and B7.2 (CD86).
    [Show full text]
  • Immunomodulation by Thalidomide and Thalidomide Analogues
    Ann Rheum Dis 1999;58:(Suppl I) I107–I113 I107 Ann Rheum Dis: first published as 10.1136/ard.58.2008.i107 on 1 November 1999. Downloaded from Immunomodulation by thalidomide and thalidomide analogues Laura G Corral, Gilla Kaplan Tumour necrosis factor á (TNFá), a key stimulate the anti-inflammatory cytokine IL10. cytokine involved in the host immune re- Similarly to thalidomide, these drugs that do sponse, also contributes to the pathogenesis of not inhibit PDE4 act as costimulators of T cells both infectious and autoimmune diseases. To but are much more potent than the parent ameliorate the pathology resulting from TNFá drug. The distinct immunomodulatory activity in these clinical settings, strategies for the inhi- of these new TNFá inhibitors may potentially bition of this cytokine have been developed. allow them to be used in the clinic for the Our previous work has shown that the drug treatment of a wide variety of immunopatho- thalidomide is a partial inhibitor of TNFá pro- logical disorders of diVerent aetiologies. duction in vivo. For example, when leprosy patients suVering from erythema nodosum TNFá is a key player in the immune leprosum (ENL) are treated with thalidomide, response the increased serum TNFá concentrations TNFá is a pleiotropic cytokine produced characteristic of this syndrome are reduced, primarily by monocytes and macrophages, but with a concomitant improvement in clinical also by lymphocytes and NK cells. TNFá plays symptoms. Similarly, we have found that in a central part in the host immune response to patients with tuberculosis, with or without HIV viral, parasitic, fungal and bacterial infections.
    [Show full text]
  • The Immunological Synapse and CD28-CD80 Interactions Shannon K
    © 2001 Nature Publishing Group http://immunol.nature.com ARTICLES The immunological synapse and CD28-CD80 interactions Shannon K. Bromley1,Andrea Iaboni2, Simon J. Davis2,Adrian Whitty3, Jonathan M. Green4, Andrey S. Shaw1,ArthurWeiss5 and Michael L. Dustin5,6 Published online: 19 November 2001, DOI: 10.1038/ni737 According to the two-signal model of T cell activation, costimulatory molecules augment T cell receptor (TCR) signaling, whereas adhesion molecules enhance TCR–MHC-peptide recognition.The structure and binding properties of CD28 imply that it may perform both functions, blurring the distinction between adhesion and costimulatory molecules. Our results show that CD28 on naïve T cells does not support adhesion and has little or no capacity for directly enhancing TCR–MHC- peptide interactions. Instead of being dependent on costimulatory signaling, we propose that a key function of the immunological synapse is to generate a cellular microenvironment that favors the interactions of potent secondary signaling molecules, such as CD28. The T cell receptor (TCR) interaction with complexes of peptide and as CD2 and CD48, which suggests that CD28 might have a dual role as major histocompatibility complex (pMHC) is central to the T cell an adhesion and a signaling molecule4. Coengagement of CD28 with response. However, efficient T cell activation also requires the partici- the TCR has a number of effects on T cell activation; these include pation of additional cell-surface receptors that engage nonpolymorphic increasing sensitivity to TCR stimulation and increasing the survival of ligands on antigen-presenting cells (APCs). Some of these molecules T cells after stimulation5. CD80-transfected APCs have been used to are involved in the “physical embrace” between T cells and APCs and assess the temporal relationship of TCR and CD28 signaling, as initiat- are characterized as adhesion molecules.
    [Show full text]
  • Induces Antigen Presentation in B Cells Cell-Activating Factor of The
    B Cell Maturation Antigen, the Receptor for a Proliferation-Inducing Ligand and B Cell-Activating Factor of the TNF Family, Induces Antigen Presentation in B Cells This information is current as of September 27, 2021. Min Yang, Hidenori Hase, Diana Legarda-Addison, Leena Varughese, Brian Seed and Adrian T. Ting J Immunol 2005; 175:2814-2824; ; doi: 10.4049/jimmunol.175.5.2814 http://www.jimmunol.org/content/175/5/2814 Downloaded from References This article cites 54 articles, 36 of which you can access for free at: http://www.jimmunol.org/content/175/5/2814.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 27, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology B Cell Maturation Antigen, the Receptor for a Proliferation-Inducing Ligand and B Cell-Activating Factor of the TNF Family, Induces Antigen Presentation in B Cells1 Min Yang,* Hidenori Hase,* Diana Legarda-Addison,* Leena Varughese,* Brian Seed,† and Adrian T.
    [Show full text]
  • Iotest CD86 (B7-2)-PC7
    IOTest CD86 (B7-2)-PC7 PN B30648 – 0.5 mL – Liquid – Clone HA5.2B7 Analyte Specific Reagent. Analytical and performance characteristics are not established. SPECIFICITY REAGENT CONTENTS SELECTED RESEARCH REFERENCES The anti-human HA5.2B7 monoclonal This antibody is provided in phosphate- 1. Rennert, P., Furlong, K., Jellis, C., antibody (mAb) binds specifically to CD86 buffered saline, containing 0.1% sodium Greenfield, E., Freeman, G.J., Ueda, Y, (B7-2) antigen (1). azide and 2 mg/mL bovine serum albumin. Levine, B., June, C.H. and Gray, G.S. The CD86 antigen (B7-2, B70) is a single Concentration: See lot specific Certificate of “The IgV domain of human B7-2 chain transmembrane glycoprotein, Analysis at www.beckmancoulter.com. (CD86) is sufficient to co-stimulate T structurally similar to CD80 (B7-1) (2, 3). Its lymphocytes and induce cytokine molecular weight is 80 kDa, under reducing STATEMENTS OF WARNING secretion”, International Immunology, conditions. The extracellular region is 1. This reagent contains 0.1% sodium 1997, 9, 6, 805–813. composed of one V-type and one C-type Ig- azide. Sodium azide under acid 2. Boussiotis, V.A., Freeman, G.J., like domains. There are 8 potential sites for conditions yields hydrazoic acid, an Gribben, J.G., Daley, J., Gray, G., N-glycosylation. The cytoplasmic tail has 3 extremely toxic compound. Azide Nadler, L.M., "Activated human B potential sites for protein kinase C compounds should be flushed with lymphocytes express three CTLA-4 phosphorylation (4, 5). CD86 shares with running water while being discarded. counterreceptors that costimulate T-cell CD80 the same co-receptors on T cells, These precautions are recommended activation", 1993, Proc.
    [Show full text]
  • Cells Expressing Truncated Major Histocompatibility Complex
    Proc. Natl. Acad. Sci. USA Vol. 90, pp. 5687-5690, June 1993 Immunology Constitutive expression of B7 restores immunogenicity of tumor cells expressing truncated major histocompatibility complex class II molecules (CD28/tumor immunity) SIVASUBRAMANIAN BASKAR*, SUZANNE OSTRAND-ROSENBERG*t, NASRIN NABAVIt, LEE M. NADLER§, GORDON J. FREEMAN§, AND LAURIE H. GLIMCHER¶ *Department of Biological Sciences, University of Maryland, Baltimore, MD 21228; *Department of Immunopharmacology, Roche Research Center, Nutley, NJ 07110-1199; §Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115; and lDepartment of Cancer Biology, Harvard School of Public Health, and Department of Medicine, Harvard Medical School, Boston, MA 02115 Communicated by Leroy Hood, March 12, 1993 ABSTRACT The inability of the autologous host to reject B7 coactivation signal. Immunization with such engineered resident tumor cells is frequently the result of inadequate tumor cells generates potent tumor-specific CD4+ T cells that generation of tumor-specific T cells. Specific activation of T facilitate rejection and confer immunologic memory to high- cells occurs after delivery of two signals by the antigen- dose challenges of wild-type neoplastic cells. These results presenting cell. The first signal is antigen-specific and is the demonstrate the critical role ofthe B7 costimulatory pathway engagement of the T-cell antigen receptor by a specific major in stimulating tumor-specific CD4+ T cells and provide an histocompatiblity complex antigen-peptide complex. For some attractive strategy for enhancing tumor immunity. T cells, the second or costimulatory signal is the interaction of the T-cell CD28 receptor with the B7 activation molecule of the antigen-presenting cell.
    [Show full text]