Prevention of acute allograft rejection by antibody targeting of TIRC7, a novel T cell membrane protein.
A novel 75 kDa membrane protein, TIRC7, is described that exhibits a central role in T cell activation in vitro and in vivo. Modulation of TIRC7-mediated signals with specific anti-TIRC7 antibodies in vitro efficiently prevents human T cell proliferation and IL-2 secretion. Moreover, anti-TIRC7 antibodies specifically inhibit type 1 subset specific IFN-gamma expression but spare the type 2 cytokine IL-4. Diminished proliferation but not IFN-gamma secretion is reversible by exogenous rIL-2. An anti-TIRC7 antibody that cross-reacts with the 75 kDa rat homolog exhibits inhibition of rat alloimmune response in vitro and significantly prolongs kidney allograft survival in vivo. Targeting of TIRC7 may provide a novel therapeutic approach for modulation of the immune response.
Utku
N
N
Institut für Medizinische Immunologie, Campus Mitte, Humboldt Universität zu Berlin, Germany. nalan.utku@charite.de
Heinemann
T
T
Tullius
S G
SG
Bulwin
G C
GC
Beinke
S
S
Blumberg
R S
RS
Beato
F
F
Randall
J
J
Kojima
R
R
Busconi
L
L
Robertson
E S
ES
Schülein
R
R
Volk
H D
HD
Milford
E L
EL
Gullans
S R
SR
D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous; D025262:Vacuolar Proton-Translocating ATPases
D000906:Antibodies; D017931:DNA Primers; D018076:DNA, Complementary; D007376:Interleukin-2; D008565:Membrane Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; C472421:TCIRG1 protein, human; D025262:Vacuolar Proton-Translocating ATPases