Cited by 1,685T-cell and B-cell ImmunologyImmunotherapy and Immune ResponsesCancer Immunotherapy and Biomarkers

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CTLA-4 is a second receptor for the B cell activation antigen B7.

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Linsley, P S, Brady, W, Urnes, M, Grosmaire, L S, Damle, N K, Ledbetter, J A·1991·The Journal of experimental medicine

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Abstract

Functional interactions between T and B lymphocytes are necessary for optimal activation of an immune response. Recently, the T lymphocyte receptor CD28 was shown to bind the B7 counter-receptor on activated B lymphocytes, and subsequently to costimulate interleukin 2 production and T cell proliferation. CTLA-4 is a predicted membrane receptor from cytotoxic T cells that is homologous to CD28 and whose gene maps to the same chromosomal band as the gene for CD28. It is not known, however, if CD28 and CTLA-4 also share functional properties. To investigate functional properties of CTLA-4, we have produced a soluble genetic fusion between the extracellular domain of CTLA-4 and an immunoglobulin C gamma chain. Here, we show that the fusion protein encoded by this construct, CTLA4Ig, bound specifically to B7-transfected Chinese hamster ovary cells and to lymphoblastoid cells. CTLA4Ig also immunoprecipitated B7 from cell surface 125I-labeled extracts of these cells. The avidity of 125I-labeled B7Ig fusion protein for immobilized CTLA4Ig was estimated (Kd approximately 12 nM). Finally, we show that CTLA4Ig was a potent inhibitor of in vitro immune responses dependent upon cellular interactions between T and B lymphocytes. These findings provide direct evidence that, like its structural homologue CD28, CTLA-4 is able to bind the B7 counter-receptor on activated B cells. Lymphocyte interactions involving the B7 counter-receptor are functionally important for alloantigen responses in vitro.

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Saiki, R. K., Scharf, S., Faloona, F., Mullis, K. B., Horn, G. T., Erlich, H. A., & Arnheim, N. (1985) · Science · doi:10.1126/science.2999980 · Cited by 8,956
Adhesion receptors of the immune system
Springer, T. A. (1990) · Nature · doi:10.1038/346425a0 · Cited by 6,477
Approaching the asymptote? Evolution and revolution in immunology.Preprint
Janeway, C. (1989) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1989.054.01.003 · Cited by 3,396
The Immunoglobulin Superfamily: Domains For Cell Surface Recognition
Williams, A., & Barclay, A. N. (1988) · Annual Review of Immunology · doi:10.1146/annurev.iy.06.040188.002121 · Cited by 2,270
A cell culture model for T lymphocyte clonal anergy
Schwartz, R. H. (1990) · Science · doi:10.1126/science.2113314 · Cited by 1,857
A Theory of Self-Nonself Discrimination
Bretscher, P., & Cohn, M. (1970) · Science · doi:10.1126/science.169.3950.1042 · Cited by 1,755
A new member of the immunoglobulin superfamily—CTLA-4
Brunet, J., Denizot, F., Luciani, M., Roux-Rouquié, M., Suzan, M., Mattéi, M., & Golstein, P. (1987) · Nature · doi:10.1038/328267a0 · Cited by 1,307
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Linsley, P. S., Brady, W., Grosmaire, L. S., Aruffo, A. A., Damle, N. K., & Ledbetter, J. A. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.173.3.721 · Cited by 1,126
Self-citation
Regulation of Lymphokine Messenger RNA Stability by a Surface-Mediated T Cell Activation Pathway
Lindstein, T., June, C. H., Ledbetter, J. A., Stella, G. C. L., & Thompson, C. B. (1989) · Science · doi:10.1126/science.2540528 · Cited by 866
Self-citation
Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system.
Aruffo, A. A., & Seed, B. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.23.8573 · Cited by 787

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Antibody to the ligand of CD40, gp39, blocks the occurrence of the acute and chronic forms of graft-vs-host disease.
Durie, F. H., Aruffo, A. A., Ledbetter, J. A., Crassi, K. M., Green, W. R., Fast, L. D., & Noelle, R. J. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117453 · Cited by 180
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Abatacept
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Scalapino, K. J., & Daikh, D. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00639.x · Cited by 177
“As with CD28, CTLA-4 has less affinity for CD86 compared with CD80 (7, 23).”
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Stoll, M. L., & Cron, R. Q. (2014) · Pediatric Rheumatology · doi:10.1186/1546-0096-12-13 · Cited by 176
“Abatacept is a soluble fusion protein consisting of the Cytotoxic T cell Lymphocyte Antigen-4 fused with the Fc region of human IgG [66].”
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The role of B7 costimulation in T‐cell immunity
Harris, N. L., & Ronchese, F. (1999) · Immunology and Cell Biology · doi:10.1046/j.1440-1711.1999.00835.x · Cited by 175
Naturally occurring regulatory T cells: markers, mechanisms, and manipulation
Schmetterer, K. G., Neunkirchner, A., & Pickl, W. F. (2012) · The FASEB Journal · doi:10.1096/fj.11-193672 · Cited by 174
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Chang, J. T., Segal, B. M., Nakanishi, K., Okamura, H., & Shevach, E. M. (2000) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(200004)30:4 · Cited by 159
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Lee, J. B., Kim, H. R., & Ha, S. (2022) · Immune Network · doi:10.4110/in.2022.22.e2 · Cited by 175
“In 2017, in vitro biochemical experiment and in vivo mouse experiment showed that SHP-2, in response to the trigger of PD-1 signal by PD-L1, inhibits CD28 co-stimulation- https://doi.org/10.4110/in.2022.22.e2 11/22https://immunenetwork.org mediated phosphorylation rather than TCR-medicated phosphorylation (109,110).”
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“Blockade of this pathway has been shown to induce specific T-cell anergy in vitro (3), and to inhibit autoimmune (12–16) and alloimmune responses in vivo.”
Background
The Role of Novel T Cell Costimulatory Pathways in Autoimmunity and Transplantation
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Niu, Z., Jin, R., Zhang, Y., & Li, H. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01200-x · Cited by 185
A reassessment of the role of B7-1 expression in tumor rejection.
Wu, T. ‐., Huang, A. Y.-C., Jaffee, E. M., Levitsky, H. I., & Pardoll, D. M. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.182.5.1415 · Cited by 170
GAD65-reactive T cells are activated in patients with autoimmune type 1a diabetes
Viglietta, V., Kent, S. C., Orban, T., & Hafler, D. A. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14114 · Cited by 170
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Influential
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The role of the T cell costimulator B7-1 in autoimmunity and the induction and maintenance of tolerance to peripheral antigen
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Ameen, R. M., Alshemmari, S., Al-Humood, S. A., Chowdhury, R. I., Al‐Eyaadi, O., & Al‐Bashir, A. (2003) · Transfusion · doi:10.1046/j.1537-2995.2003.00549.x · Cited by 169
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Th2 cell clonal anergy as a consequence of partial activation.
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Result
Differential expression of CTLA-4 among T cell subsets
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Schneider, H. E., Prasad, K. V., Shoelson, S. E., & Rudd, C. E. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.1.351 · Cited by 164
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BackgroundResultInfluentialSelf-citation
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Cross, A. H., Girard, T. J., Giacoletto, K. S., Evans, R. J., Keeling, R. M., Lin, R. F., Trotter, J. L., & Karr, R. W. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117982 · Cited by 155
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“org Clin Cancer Res 2007;13(3) February1, 2007 960”
Influential
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“[5, 6]”
Signal transduction events leading to T-cell lymphokine gene expression
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Background
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Stein, P. H., Fraser, J. D., & Weiss, A. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.5.3392 · Cited by 148
Expression of CD27 and its ligand, CD70, on chronic lymphocytic leukemia B cells
Ranheim, E. A., Cantwell, M., & Kipps, T. J. (1995) · Blood · doi:10.1182/blood.v85.12.3556.bloodjournal85123556 · Cited by 148
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Arigami, T., Narita, N., Mizuno, R., Nguyen, L., Ye, X., Chung, A. P., Giuliano, A. E., & Hoon, D. S. �. (2010) · Annals of Surgery · doi:10.1097/sla.0b013e3181f1939d · Cited by 144
“Negative 22 (82) 10 (59) 7 (33) 40 (61) 0.”
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McLellan, A. D., Sorg, R. V., Williams, L. A., & Hart, D. N. J. (1996) · European Journal of Immunology · doi:10.1002/eji.1830260603 · Cited by 146
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Ranger, A. M., Das, M. P., Kuchroo, V. K., Glimcher, L. H., & Ploegh, H. L. (1996) · International Immunology · doi:10.1093/intimm/8.10.1549 · Cited by 145
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Kennedy, M. K., Mohler, K. M., Shanebeck, K. D., Baum, P. R., Picha, K. S., Otten-Evans, C., Janeway, C. A., & Grabstein, K. H. (1994) · European Journal of Immunology · doi:10.1002/eji.1830240118 · Cited by 142
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Peach, R., Bajorath, J., Naemura, J. R., Leytze, G., Greene, J. L., Aruffo, A. A., & Linsley, P. S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.36.21181 · Cited by 140
Self-citation
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de Boer, M., Kasran, A., Kwekkeboom, J., Walter, H., Vandenberghe, P., & Ceuppens, J. L. (1993) · European Journal of Immunology · doi:10.1002/eji.1830231212 · Cited by 140
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Activation of human peripheral blood dendritic cells induces the CD86 co‐stimulatory molecule
McLellan, A. D., Starling, G. C., Williams, L. A., Hock, B. D., & Hart, D. N. J. (1995) · European Journal of Immunology · doi:10.1002/eji.1830250739 · Cited by 136
Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model.
Krinzman, S. J., Sanctis, G. T. D., Cernadas, M., Mark, D. A., Wang, Y., Listman, J. A., Kobzik, L., Donovan, C., Nassr, K., Katona, I. M., et al. (1996) · Journal of Clinical Investigation · doi:10.1172/jci119093 · Cited by 136
Combination of Radiotherapy and Immune Checkpoint Inhibitors
Pilones, K. A., Vanpouille‐Box, C., & Demaria, S. (2014) · Seminars in Radiation Oncology · doi:10.1016/j.semradonc.2014.07.004 · Cited by 140
Production and characterization of transgenic pigs expressing porcine CTLA4‐Ig
Phelps, C. J., Ball, S. F., Vaught, T. D., Vance, A., Mendicino, M., Monahan, J., Walters, A. H., Wells, K. D., Dandro, A. S., Ramsoondar, J., et al. (2009) · Xenotransplantation · doi:10.1111/j.1399-3089.2009.00533.x · Cited by 135
“One of these co-stimulatory interactions occurs between CD28 (on the surface of T cells) and the B7 ligands, CD80 and CD86 (on antigen-presenting cells).”
BackgroundInfluential
Immunotherapy earns its spot in the ranks of cancer therapy
Pardoll, D. M., & Drake, C. G. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20112275 · Cited by 134
Population Pharmacokinetics and Pharmacodynamics of the Anti-CD11a Antibody hu1124 in Human Subjects with Psoriasis
Bauer, R. J., Dedrick, R. L., White, M., Murray, M. J., & Garovoy, M. R. (1999) · Journal of Pharmacokinetics and Biopharmaceutics · doi:10.1023/a:1020917122093 · Cited by 135
“Another molecule that also interferes with T cell-antigen presenting cell recognition is CTLA4Ig, a recombinant chimeric protein where the variable region of human IgGl has been replaced with the extracellular domain of CTLA4 (19).”
Background
Beyond T-Cells: Functional Characterization of CTLA-4 Expression in Immune and Non-Immune Cell Types
Oyewole-Said, D., Konduri, V., Vazquez‐Perez, J., Weldon, S. A., Levitt, J. M., & Decker, W. K. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.608024 · Cited by 144
“2 (B7 proteins) (2, 3), these molecules mediate opposing effects on T-cell function.”
Background
Differential expression and function of CD80 (B7‐1) and CD86 (B7‐2) on human peripheral blood monocytes
FLEISCHER, J., Soeth, E., Reiling, N., Grage‐Griebenow, E., Flad, H.-D., & Ernst, M. (1996) · Immunology · doi:10.1046/j.1365-2567.1996.d01-785.x · Cited by 134
COMBINED COSTIMULATION BLOCKADE PLUS RAPAMYCIN BUT NOT CYCLOSPORINE PRODUCES PERMANENT ENGRAFTMENT1
Li, Y., Zheng, X. X., Li, X. C., Zand, M. S., & Strom, T. B. (1998) · Transplantation · doi:10.1097/00007890-199811270-00021 · Cited by 134
Co‐stimulation of murine CD4 T cell growth: cooperation between B7 and heat‐stable antigen
Liu, Y., Jones, B., Brady, W., Janeway, C. A., & Linley, P. S. (1992) · European Journal of Immunology · doi:10.1002/eji.1830221115 · Cited by 134
Self-citation
Recurrent activating mutations of CD28 in peripheral T-cell lymphomas
Rohr, J. M., Guo, S., Huo, J., Bouska, A. C., Lachel, C. M., Li, Y., Simone, P. D., Zhang, W., Gong, Q., Wang, C., et al. (2015) · Leukemia · doi:10.1038/leu.2015.357 · Cited by 138
Tim-3, Lag-3, and TIGIT
Joller, N., & Kuchroo, V. K. (2017) · Current topics in microbiology and immunology · doi:10.1007/82_2017_62 · Cited by 145
Solution structure of human CTLA-4 and delineation of a CD80/CD86 binding site conserved in CD28
Metzler, W. J., Bajorath, J., Fenderson, W., Shaw, S., Constantine, K. L., Naemura, J. R., Leytze, G., Peach, R., Lavoie, T., Mueller, L., et al. (1997) · Nature Structural Biology · doi:10.1038/nsb0797-527 · Cited by 133
Self-citation
A quantitative analysis of antigen-presenting cell function: activated B cells stimulate naive CD4 T cells but are inferior to dendritic cells in providing costimulation.
Cassell, D. J., & Schwartz, R. H. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.180.5.1829 · Cited by 133
Soluble CD86 Is a Costimulatory Molecule for Human T Lymphocytes
Jeannin, P., Magistrelli, G., Aubry, J., Caron, G., Gauchat, J., Renno, T., Herbault, N., Goetsch, L., Blaecke, A., Dietrich, P., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)00030-3 · Cited by 131
Orchestrating immune check-point blockade for cancer immunotherapy in combinations
Perez‐Gracia, J. L., Labiano, S., Rodriguez-Ruiz, M. E., Sanmamed, M. F., & Melero, I. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.01.002 · Cited by 131
“CTLA-4 CTLA-4 (CD152) was identified as a closely related CD28 homolog [6] whose T-cell restricted transcription was induced from zero levels after activation [7].”
B7 Expression on T Cells Down-Regulates Immune Responses through CTLA-4 Ligation via R-T Interactions
Taylor, P. A., Lees, C. J., Fournier, S., Allison, J. P., Sharpe, A. H., & Blazar, B. R. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.1.34 · Cited by 130
“Although CD28 is constitutively expressed on T cells and CTLA-4 is expressed on cell surface only after T cell activation, CTLA-4 has a higher binding affinity for B7-1 and B7-2 than does CD28 and functions to down-regulate T cell responses (2, 18).”
Background
"Anergy" of TH0 helper T lymphocytes induces downregulation of TH1 characteristics and a transition to a TH2-like phenotype.
Gajewski, T. F., Lancki, D. W., Stack, R. M., & Fitch, F. W. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.2.481 · Cited by 129
Distinct Costimulatory Molecules Are Required for the Induction of Effector and Memory Cytotoxic T Lymphocytes
Liu, Y., Wenger, R. H., Zhao, M., & Nielsen, P. J. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.2.251 · Cited by 129
B cell function in mice transgenic for mCTLA4-H gamma 1: lack of germinal centers correlated with poor affinity maturation and class switching despite normal priming of CD4+ T cells.
Lane, P. J. L., Burdet, C., Hubele, S., Scheidegger, D., Müller, U., McConnell, F. M., & Kosco‐Vilbois, M. H. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.3.819 · Cited by 129
T-cell activation: integration of signals from the antigen receptor and costimulatory molecules
Robey, E. A., & Allison, J. P. (1995) · Immunology Today · doi:10.1016/0167-5699(95)80140-5 · Cited by 129
Combinatorial prospects of nano-targeted chemoimmunotherapy
Silva, C. G. D., Rueda, F., Löwik, C. W. G. M., OSSENDORP, F. A., & Cruz, L. J. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.01.006 · Cited by 128
Recent advances in graft‐versus‐host disease (GVHD) prevention
Blazar, B. R., Korngold, R., & Daniel, A. R. (1997) · Immunological Reviews · doi:10.1111/j.1600-065x.1997.tb00976.x · Cited by 131
Murine B7 antigen provides an efficient costimulatory signal for activation of murine T lymphocytes via the T-cell receptor/CD3 complex.
Reiser, H., Freeman, G. J., Razi-Wolf, Z., Gimmi, C. D., D, B. B. M., & Nadler, L. M. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.1.271 · Cited by 128
A Closer Look at Homeostatic Proliferation of CD4+ T Cells: Costimulatory Requirements and Role in Memory Formation
Guðmundsdóttir, H., & Turka, L. A. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.7.3699 · Cited by 129
CTLA-4 is not restricted to the lymphoid cell lineage and can function as a target molecule for apoptosis induction of leukemic cells
Pistillo, M. P. (2002) · Blood · doi:10.1182/blood-2002-06-1668 · Cited by 127
The V domain of herpesvirus Ig-like receptor (HIgR) contains a major functional region in herpes simplex virus-1 entry into cells and interacts physically with the viral glycoprotein D
Cocchi, F., Lopez, M., Menotti, L., Aoubala, M., Dubreuil, P. C., & Campadelli‐Fiume, G. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15700 · Cited by 127
Mice transgenic for a soluble form of murine CTLA-4 show enhanced expansion of antigen-specific CD4+ T cells and defective antibody production in vivo.
Ronchese, F., Hausmann, B., Hubele, S., & Lane, P. J. L. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.3.809 · Cited by 125
Complete blockade of B7 family-mediated costimulation is necessary to induce human alloantigen-specific anergy: a method to ameliorate graft- versus-host disease and extend the donor pool
Gribben, J. G., Guinan, E., Boussiotis, V., Ke, X., Linsley, L., Sieff, C. A., Gray, G., Freeman, G., & Nadler, L. M. (1996) · Blood · doi:10.1182/blood.v87.11.4887.bloodjournal87114887 · Cited by 127
T-Cell Costimulatory Pathways in Allograft Rejection and Tolerance
Clarkson, M. R., & Sayegh, M. H. (2005) · Transplantation · doi:10.1097/01.tp.0000168432.60022.99 · Cited by 126
Peptide Antigen Priming of Naive, But Not Memory, CD8 T Cells Requires a Third Signal That Can Be Provided by IL-12
Schmidt, C. S., & Mescher, M. F. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.11.5521 · Cited by 123
“CTLA4-Ig binds to B7-1 and B7-2 with high affinity and prevents CD28 from binding to them (24).”
Background

Authors: Linsley, P. S., Brady, W., Urnes, M., Grosmaire, L. S., Damle, N. K., & Ledbetter, J. A.
Affiliations: Bristol-Myers Squibb (United States) (US)
ORCID: Linsley, P S
Venue: The Journal of experimental medicine
Publisher: Rockefeller University Press
Published: 1991-09-01
Volume: 174
Issue: 3
Pages: 561-569
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.174.3.561
PMC: PMC2118936
OpenAlex: W2087013294
Cited by: 1,685
References: 41
Citations by year: 2026: 14 · 2025: 31 · 2024: 49 · 2023: 37 · 2022: 35 · 2021: 49 · 2020: 51 · 2019: 55 · 2018: 49 · 2017: 49 · 2016: 59 · 2015: 52 · 2014: 39 · 2013: 41 · 2012: 39
FWCI: 27.78
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journal of Experimental Medicine (publishedVersion)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Funders: Bristol-Myers Squibb
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords: CTLA-4, B7, CD28, T cell costimulation, B cell activation, T cell-B cell interaction, soluble receptor, interleukin-2, alloantigen response, cytotoxic T lymphocytes
MeSH terms: Abatacept, Amino Acid Sequence, Animals, Antigens, Differentiation, Antigens, Surface, B-Lymphocytes, Base Sequence, Cell Line, Ligands, Lymphocyte Cooperation, Lymphocyte Activation, Molecular Sequence Data, Oligonucleotides, Precipitin Tests, Receptors, Immunologic, Recombinant Fusion Proteins, T-Lymphocytes, Antigens, CD, B7-1 Antigen, Immunoconjugates, CTLA-4 Antigen, In Vitro Techniques

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CTLA-4 is a second receptor for the B cell activation antigen B7.

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