Evidence for an additional ligand, distinct from B7, for the CTLA-4 receptor.
Activation of T lymphocytes requires the recognition of peptide-major histocompatibility complex complexes and costimulatory signals provided by antigen-presenting cells (APCs). The best-characterized costimulatory molecule to date is the B7 antigen, a member of the immunoglobulin family that binds two receptors, CD28 and CTLA-4, expressed on the T-cell surface. Using the anti-mouse B7 (mB7) monoclonal antibody (mAb) 16-10A1, which we recently developed, we found that mB7 is indeed an important costimulatory ligand for the antigen-specific activation of murine T cells by B lymphocytes. Three lines of evidence suggest, however, the existence of at least one additional ligand for the CTLA-4 receptor. First, a soluble fusion protein of human CTLA-4 and the IgG1 Fc region, termed CTLA4Ig, blocks better than the anti-mB7 mAb the allogeneic stimulation of T cells by unfractionated splenic APCs. Second, saturating amounts of anti-mB7 mAb do not significantly block binding of fluorescein isothiocyanate-conjugated CTLA4Ig to activated splenic APCs. Furthermore, CTLA4Ig but not the anti-mB7 mAb reacts with the M12 and M12.C3 cell lines. The identification of an additional ligand for CTLA-4 may have applications to the treatment of autoimmune disease and transplant-associated disorders.
Razi-Wolf
Z
Z
Division of Lymphocyte Biology, Dana-Farber Cancer Institute, Boston, MA 02115.
Galvin
F
F
Gray
G
G
Reiser
H
H
D000069594:Abatacept; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism; D060908:CTLA-4 Antigen; D018796:Immunoconjugates; D066298:In Vitro Techniques; D008024:Ligands; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D051379:Mice; D013154:Spleen / Q000166:cytology
D000941:Antigens; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D008024:Ligands; D000069594:Abatacept