A native soluble form of CTLA-4.
CTLA-4 is an immunoregulatory receptor expressed on the surface of activated T and B lymphocytes. The counterreceptors for CTLA-4 are the B7 family molecules. We describe alternatively spliced mRNAs expressed in hematolymphoid tissues of humans, mice, and rats that lack the transmembrane domain coded by exon 3 of the CTLA-4 gene. These alternate transcripts were detected by RT-PCR in B cells and resting T cells of both the CD4 and the CD8 phenotype. Activation of human blood mononuclear cells with PHA or anti-CD3 + anti-CD28 monoclonal antibodies appears to effect a decrease in the amount of the alternative transcript relative to the full-length transcript. Recombinant sCTLA-4 is a B7-binding protein and has immunomodulatory effects as measured by inhibition of the mixed leukocyte response. Human serum contains immunoreactive material consistent with a native soluble form of CTLA-4.
Oaks
M K
MK
Transplant Research Laboratory, St. Luke's Medical Center, Milwaukee, WI 53215, USA. Moaks@execpc.com
Hallett
K M
KM
Penwell
R T
RT
Stauber
E C
EC
Warren
S J
SJ
Tector
A J
AJ
D000069594:Abatacept; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000097:blood / Q000235:genetics*; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D001483:Base Sequence; D060908:CTLA-4 Antigen; D003001:Cloning, Molecular; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates; D008221:Lymphoid Tissue / Q000276:immunology; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000302:isolation & purification; D051381:Rats; D011971:Receptors, Immunologic / Q000097:blood / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012995:Solubility
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C497965:Cd86 protein, mouse; C497966:Cd86 protein, rat; C556707:Ctla4 protein, mouse; C556708:Ctla4 protein, rat; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D000069594:Abatacept