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(Siglec) Adhesion Receptor That Binds CD83

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(Siglec) Adhesion Receptor That Binds CD83 CD83 Is a Sialic Acid-Binding Ig-Like Lectin (Siglec) Adhesion Receptor that Binds Monocytes and a Subset of Activated CD8+ T Cells This information is current as of September 25, 2021. Nathalie Scholler, Martha Hayden-Ledbetter, Karl-Erik Hellström, Ingegerd Hellström and Jeffrey A. Ledbetter J Immunol 2001; 166:3865-3872; ; doi: 10.4049/jimmunol.166.6.3865 http://www.jimmunol.org/content/166/6/3865 Downloaded from References This article cites 44 articles, 21 of which you can access for free at: http://www.jimmunol.org/content/166/6/3865.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 25, 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 Errata An erratum has been published regarding this article. Please see next page or: /content/182/3/1772.2.full.pdf 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 © 2001 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. CD83 Is a Sialic Acid-Binding Ig-Like Lectin (Siglec) Adhesion Receptor that Binds Monocytes and a Subset of Activated CD8؉ T Cells1 Nathalie Scholler,2* Martha Hayden-Ledbetter,† Karl-Erik Hellstro¨m,* Ingegerd Hellstro¨m,* and Jeffrey A. Ledbetter† To help determine CD83 function, a cDNA encoding a soluble protein containing the CD83 extracellular domain was fused with a mutated human IgG1 constant region (CD83Ig) and expressed by stable transfection of Chinese hamster ovary cells. Purified .CD83Ig bound to peripheral blood monocytes and a subset of activated CD3؉CD8؉ lymphocytes but did not bind to FcR Monocytes that had adhered to plastic lost their ability to bind to CD83Ig after 90 min of in vitro incubation. CD83Ig bound to two of five T cell lines tested, HPB-ALL and Jurkat. The binding to HPB-ALL cells significantly increased when they were grown Downloaded from at a low pH (pH 6.5), whereas binding to Jurkat cells increased after apoptosis was induced with anti-Fas mAb. B cell and monocytic lines did not bind CD83Ig and neither did CD56؉ NK cells or granulocytes. Full-length CD83 expressed by a transfected carcinoma line mediated CD83-dependent adhesion to HPB-ALL cells. CD83Ig immunoprecipitated and immunoblotted a 72-kDa protein from HPB-ALL cells. Binding of CD83Ig to HPB-ALL cells was eliminated by neuraminidase treatment of the cells. We conclude that CD83 is an adhesion receptor with a counterreceptor expressed on monocytes and a subset of activated or stressed T lymphocytes, and that interaction between CD83 and its counterreceptor is dependent upon the state of glycosylation of a 72-kDa http://www.jimmunol.org/ counterreceptor by sialic acid residues. In view of the selectivity of the expression of CD83 and its ligand, we postulate that the interaction between the two plays an important role in the induction and regulation of immune responses. The Journal of Immunology, 2001, 166: 3865–3872. he marker CD83 is highly restricted to mature dendritic that includes B-G, butyrophilin, MOG, BT, BT2, B7c, B7-1, and cells (DC),3 including Langerhans cells and interdigitat- B7-2 (8–11). However, its function is not known. We now present T ing reticulum cells in the T cells zones of lymphoid or- data suggesting that CD83 mediates adhesion of DC to circulating gans (1, 2). It was independently discovered by two different monocytes and to a fraction of activated T cells or stressed T cells teams, in 1992 by Zhou et al. (2) and in 1993 by Kozlow et al. (3). by a specific binding of CD83 to a 72-kDa counterreceptor (li- by guest on September 25, 2021 Mouse CD83 was recently cloned and is up-regulated during DC gand). We further show that CD83Ig binding to its ligand is elim- maturation (4). CD83 transcripts are also detectable in mouse and inated by neuraminidase, an enzyme specific for the most common human brain mRNA by Northern hybridization, although it is not sialic acid, N-acetylneuraminic acid. Thus, CD83Ig binds to a car- known what cells within the brain express CD83 (3, 5). bohydrate epitope that depends on sialic acid residues. This clas- Isolation of cDNA encoding CD83 revealed that it is a 45-kDa sifies CD83 as a sialic acid-binding Ig-like lectin (Siglec; Ref. 12). type 1 membrane glycoprotein member of the Ig superfamily (2). Our data further suggest that the formation of the carbohydrate It is composed of a single extracellular V-type Ig-like domain, a epitope recognized by CD83 is influenced by cell growth condi- transmembrane region, and a 40-aa short cytoplasmic domain. The tions and can be rapidly altered by cellular stress and early tran- CD83 structure is similar to that of several other members of the sition to apoptosis. Ig superfamily. CD83 shows highly restricted cellular expression, it shares 23% overall identity with myelin protein Po, the most abundant glycoprotein in the peripheral myelin of mammals (6, 7), Materials and Methods and has significant homologies with the B7 ancestral gene family CD83Ig fusion protein construction A population highly enriched for DC was isolated from 200 ml of human peripheral blood by discontinuous Nycodenz gradient centrifugation, as Laboratories of *Tumor Immunology and †Immunobiology, Pacific Northwest Re- search Institute, Seattle, WA 98122 described elsewhere (13). Nycodenz was purchased as Nycoprep (13% (w/v) Nycodenz, 0.58% (w/v) NaCl, 5 mM Tris-HCl, pH 7.2, density ϭ Received for publication September 26, 2000. Accepted for publication January 8, 1.068 Ϯ 0.001, 335 Ϯ 5 mOsm/kg) from Nycomed Pharma (Oslo, Nor- 2001. way). At the end of the purification procedure, RNA was directly extracted The costs of publication of this article were defrayed in part by the payment of page from DC by TRIzol (Life Technologies, Grand Island, NY) and reverse charges. This article must therefore be hereby marked advertisement in accordance transcripted (Superscript II; Life Technologies). cDNA from DC was am- with 18 U.S.C. Section 1734 solely to indicate this fact. plified with PCR primers containing a 5Ј HindIII site: gaataagctt atg tcg cgc 1 This work was supported by Pacific Northwest Research Institute and by National ggc ctc cag ctt ctg ctc c and a 3Ј BglII site in the antisense primer: gag cca Institutes of Health Grants CA90143 (to J.A.L.), CA79490 (to K.E.H.) and CA85780 gca gca gga gaagatctt ccg ctc tgt att tc. The PCR product (457 bp) was (to I.H.). cloned into pCDNA1 human IgG1 (a gift from Robert Peach, Bristol Myers 2 Address correspondence and reprint requests to Dr. Nathalie Scholler, Laboratory of Squibb Pharmaceutical Institute, Princeton, NJ). DNA from recombinant Tumor Immunology, Pacific Northwest Research Institute, 720 Broadway, Seattle, colonies was amplified by Qiagen plasmid maxi kit (Qiagen, Valencia, WA 98122. E-mail address: [email protected] CA), sequenced, and transfected into COS7 cells. After 3 days, the pres- 3 Abbreviations used in this paper: DC, dendritic cell; Siglec, sialic acid-binding ence of soluble protein in cell supernatant was checked by Western blot Ig-like lectin; PVDF, polyvinylidene difluoride. analysis and the fusion protein was purified by protein A-Sepharose 4B Copyright © 2001 by The American Association of Immunologists 0022-1767/01/$02.00 3866 CD83 IS A SIALIC ACID-BINDING Ig-LIKE LECTIN (SIGLEC) ADHESION RECEPTOR affinity chromatography (Zymed, South San Francisco, CA). Stable trans- DMEM medium. In some experiments, incubations were carried in DMEM fectants were generated in Chinese hamster ovaries cells by using CD83Ig medium that had been supplemented with 2-fold serial dilutions of sucrose cDNA cloned into pD18 (14). (from 0.6 to 0.1 M). CD83 retrovirus construction and generation of transfected cell Labeling of beads line A total of 50 ␮g of material to be labeled (CD83Ig, anti-CD83 mAb, and CD83 cDNA was cloned into pLNCX vector (15). DNA from recombinant a mixture of anti-CD28 mAb and anti-CD3 mAb) were conjugated to mag- colonies was amplified by Qiagen plasmid maxi kit and transfected into netic beads (Tosylativated Dynabeads M-450; Dynal, Lake Success, NY) ecotropic packaging cells (PE501) by using a calcium phosphate method according to a published protocol (19). Beads conjugated with CD83Ig or (16). PE501 viral supernatant was used to infect PG13 cells, a primate- anti-CD83 mAb were used to test the specificity of CD83Ig fusion protein. specific packaging line. PG13 supernatant was harvested, filtered, and used Anti-CD28/anti-CD3 mAb-conjugated beads were used to stimulate T to infect 1C, a colon carcinoma line derived in our laboratory. Recombi- cells. nant colonies were selected by G418 (Life Technologies). T cell stimulation with anti-CD28/anti-CD3 mAb-coated beads Media for cell culture and flow cytometry PBMC were incubated 5 days with conjugated or nonconjugated beads (control) in RPMI medium at 37°C. After that time, the beads were mag- Cells were cultured with a standard medium (referred to as RPMI medium), netically removed and the cells resuspended in RPMI medium supple- which consisted of RPMI 1640 (Life Technologies) supplemented with mented with 10 IU/ml of rIL-2 (Roche Molecular Biochemicals, Indianap- glutamine (1%; Life Technologies), penicillin/streptomycin (1%; Life olis, IN) and cultivated for 2 wk.
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