Molecular cloning and expression of early T cell costimulatory molecule-1 and its characterization as B7-2 molecule.
The interaction of T cell CD28/CTLA-4 receptors with B7-1 activation Ag on APC represents an important costimulatory pathway in T cell activation. However, it is now evident that this costimulatory pathway is neither unique nor universal for the activation of T cells. Our previous study indicated that a 60-kDa membrane protein, recognized by mAb 2D10, was expressed before B7 by activated murine B cells. This molecule was critically involved in activation of T cells in response to auto- and alloantigens. In the present study, we report on the isolation of a cDNA for this early T cell costimulatory molecule (ETC-1). ETC-1, like B7-1, is a member of the Ig supergene family and is composed of 303 amino acids. Nucleic acid sequence comparison indicated that ETC-1 is identical to the B7-2 molecule. When expressed in Chinese hamster ovary cells, ETC-1 showed profound T cell costimulatory activity as demonstrated by its ability to enhance CD4 T cell proliferation in response to Con A or anti-CD3 stimulation. Furthermore, ETC-1 also bound to both CD28-Ig and CTLA4-Ig fusion proteins. These results strongly support the notion that the interaction of ETC-1/B7-2 with CD28 or CTLA-4 receptors represents an alternative T cell costimulatory pathway.
Chen
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C
Department of Inflammation and Autoimmune Diseases, Roche Research Center, Nutley, NJ 07110.
Gault
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A
Shen
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L
Nabavi
N
N
D000069594:Abatacept; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D018122:B7-1 Antigen / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D051940:B7-2 Antigen; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016466:CHO Cells; D060908:CTLA-4 Antigen; D003001:Cloning, Molecular; D006224:Cricetinae; D018076:DNA, Complementary / Q000302:isolation & purification; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D018076:DNA, Complementary; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D003994:Bucladesine; D000069594:Abatacept