Specific interaction of lymphocyte function-associated antigen 3 with CD2 can inhibit T cell responses.
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- G T Miller
- Biogen, Inc, Cambridge, Massachusetts 02142.
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- P S Hochman
- Biogen, Inc, Cambridge, Massachusetts 02142.
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- W Meier
- Biogen, Inc, Cambridge, Massachusetts 02142.
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- R Tizard
- Biogen, Inc, Cambridge, Massachusetts 02142.
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- S A Bixler
- Biogen, Inc, Cambridge, Massachusetts 02142.
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- M D Rosa
- Biogen, Inc, Cambridge, Massachusetts 02142.
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- B P Wallner
- Biogen, Inc, Cambridge, Massachusetts 02142.
抄録
<jats:p>Accessory cell surface molecules, such as T cell antigen CD2 and its ligand lymphocyte function-associated antigen 3 (LFA-3; CD58), are critical costimulatory pathways for optimal T cell activation in response to antigens. Interaction of CD2 with cell surface LFA-3 not only increases T cell/accessory cell adhesion, but also induces signal transduction events involved in the regulation of T cell responses. In this report, we show that specific interactions of LFA-3 with CD2 can result in T cell unresponsiveness to antigenic or mitogenic stimuli in vitro. By deletion of certain regions of the extracellular domain of LFA-3, we localized the CD2 binding site to the first domain of LFA-3. We then demonstrated that a soluble, purified first domain-LFA-3/IgG1 fusion protein (LFA3TIP) interacts with CD2 and binds to the same CD2 epitope as purified multimeric or cell surface-expressed LFA-3. LFA3TIP inhibits tetanus toxoid, hepatitis B surface antigen, anti-CD3 mAb, Con A, and phytohemagglutinin P-induced T cell proliferation, as well as xenogeneic and allogeneic mixed lymphocyte reactions (MLR). Unlike anti-LFA-3 or anti-CD2 monoclonal antibodies (mAbs) which inhibit T cell responses by blocking LFA-3/CD2 binding, LFA3TIP is capable of rendering T cells unresponsive to antigenic stimuli in situations where T cell activation is independent of CD2/LFA-3 interactions. Furthermore, LFA3TIP, but not blocking anti-CD2 mAbs, is capable of inducing T cell unresponsiveness to secondary stimulation in allogeneic MLR. This inhibition of T cell responses by LFA3TIP occurs through a different mechanism from that of mAbs to LFA-3 or CD2.</jats:p>
収録刊行物
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- The Journal of experimental medicine
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The Journal of experimental medicine 178 (1), 211-222, 1993-07-01
Rockefeller University Press
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詳細情報 詳細情報について
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- CRID
- 1360574096150972288
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- NII論文ID
- 30017430532
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- ISSN
- 15409538
- 00221007
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