Murine B7-2, an alternative CTLA4 counter-receptor that costimulates T cell proliferation and interleukin 2 production.
The B7-1 molecule, expressed on antigen presenting cells (APC), provides a crucial costimulatory signal for T cell activation. Recent studies demonstrate the existence of alternative, non-B7-1 CTLA4 counter-receptors in mice and humans. Here, we describe the molecular cloning and demonstrate costimulatory function of the murine B7-2 (mB7-2) gene. Murine B7-2 cDNA encodes a member of the Ig supergene family that binds CTLA4-Ig and stains with the GL1 but not anti-mB7-1 mAb. Murine B7-2 costimulates the proliferation and interleukin 2 production of CD4+ T cells and this costimulation can be inhibited by either CTLA4-Ig or GL1 mAb. Identification of the B7-2 molecule will permit further manipulation of the B7:CD28/CTLA4 costimulatory pathway which has been shown to be involved in the prevention of tolerance, induction of tumor immunity, and most recently, in the pathogenesis of autoimmunity.
Freeman
G J
GJ
Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115.
Borriello
F
F
Hodes
R J
RJ
Reiser
H
H
Gribben
J G
JG
Ng
J W
JW
Kim
J
J
Goldberg
J M
JM
Hathcock
K
K
Laszlo
G
G
D000069594:Abatacept; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D018122:B7-1 Antigen / Q000235:genetics* / Q000378:metabolism; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D018796:Immunoconjugates; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D018076:DNA, Complementary; D018796:Immunoconjugates; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000069594:Abatacept