T-cell co-stimulation through B7RP-1 and ICOS.
T-cell activation requires co-stimulation through receptors such as CD28 and antigen-specific signalling through the T-cell antigen receptor. Here we describe a new murine costimulatory receptor-ligand pair. The receptor, which is related to CD28 and is the homologue of the human protein ICOS, is expressed on activated T cells and resting memory T cells. The ligand, which has homology to B7 molecules and is called B7-related protein-1 (B7RP-1), is expressed on B cells and macrophages. ICOS and B7RP-I do not interact with proteins in the CD28-B7 pathway, and B7RP-1 co-stimulates T cells in vitro independently of CD28. Transgenic mice expressing a B7RP-1-Fc fusion protein show lymphoid hyperplasia in the spleen, lymph nodes and Peyer's patches. Presensitized mice treated with B7RP-1-Fc during antigen challenge show enhanced hypersensitivity. Therefore, B7RP-1 exhibits co-stimulatory activities in vitro and in vivo. ICOS and B7RP-1 define a new and distinct receptor-ligand pair that is structurally related to CD28-B7 and is involved in the adaptive immune response.
Yoshinaga
S K
SK
Amgen Inc., Thousand Oaks, California 91320, USA. syoshina@amgen.com
Whoriskey
J S
JS
Khare
S D
SD
Sarmiento
U
U
Guo
J
J
Horan
T
T
Shih
G
G
Zhang
M
M
Coccia
M A
MA
Kohno
T
T
Tafuri-Bladt
A
A
Brankow
D
D
Campbell
P
P
Chang
D
D
Chiu
L
L
Dai
T
T
Duncan
G
G
Elliott
G S
GS
Hui
A
A
McCabe
S M
SM
Scully
S
S
Shahinian
A
A
Shaklee
C L
CL
Van
G
G
Mak
T W
TW
Senaldi
G
G
D000595:Amino Acid Sequence; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D019556:COS Cells; D002478:Cells, Cultured; D006224:Cricetinae; D018076:DNA, Complementary; D003877:Dermatitis, Contact / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D018076:DNA, Complementary; C556692:ICOS protein, human; C556694:Icos protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008024:Ligands; D011993:Recombinant Fusion Proteins