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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Gribben, J. G. Gray, G. Daley, J. Boussiotis, V. A. Freeman, G. J. Nadler, L. M. |
| Description | Author Affiliation: Boussiotis VA ( Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA.); |
| Abstract | Signaling via the T-cell receptor complex is necessary but not sufficient to induce antigen-specific T lymphocytes to expand clonally. To proliferate, T cells must receive one or more costimulatory signals provided by antigen presenting cells (APCs). One such critical costimulatory signal is delivered by the CD28/CTLA-4 counterreceptor, B7, expressed on APCs. B7 costimulation induces CD28 signaling, resulting in interleukin 2 (IL-2) secretion, and T-cell proliferation. Conversely, T-cell receptor signaling in the absence of B7 costimulation results in induction of antigen-specific tolerance. Here, we show that activated human B lymphocytes express two additional CTLA-4 counterreceptors also capable of providing T-cell costimulation. At 24 hr postactivation, B cells express a CTLA-4 counterreceptor not recognized by anti-B7 or -BB-1 monoclonal antibodies (mAbs), which induces detectable IL-2 secretion and T-cell proliferation. At 48 and 72 hr postactivation, B cells express both B7 and a third CTLA-4 counterreceptor identified by the anti-BB-1 mAb. BB-1 appears to be a molecule distinct from B7 by its expression on B7- cells and its capacity to induce T cells to proliferate without significant accumulation of IL-2. As observed for B7, costimulatory signals mediated by these alternative CTLA-4/CD28 counterreceptors are likely to be essential for generation of an immune response and their absence may result in antigen-specific tolerance. We propose the following terminology for these CTLA-4 counterreceptors: (i) B7, B7-1; (ii) early CTLA-4 binding counterreceptor, B7-2; and (iii) BB-1, B7-3. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 23 |
| Volume Number | 90 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1993-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antigens, Differentiation Metabolism B-Lymphocytes Immunoconjugates Receptors, Immunologic T-Lymphocytes Immunology Abatacept Antibodies, Monoclonal Antigens, CD Antigens, CD80 CTLA-4 Antigen Flow Cytometry Interleukin-2 Lymphocyte Activation Receptor Aggregation Receptors, Antigen, B-Cell Physiology Time Factors Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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