A multimeric form of soluble recombinant sheep LFA-3 (CD58) inhibits human T-cell proliferation
- Author(s)
- Yamashita, K; Parish, CR; Warren, HS; Harrison, LC;
- Details
- Publication Year 1997-09,Volume 92,Issue #1,Page 39-44
- Journal Title
- IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- The resetting of T cells by sheep erythrocytes is mediated through the interaction of the CD2 molecule on T cells with T11TS, a molecule on sheep erythrocytes homologous to lymphocyte function-associated antigen-3 (LFA-3, CD58). We cloned a T11TS cDNA from sheep leucocyte mRNA which encodes a soluble molecule comprising the distal D1 and the D2 extracellular domains, but not the transmembrane domain. cDNA for this soluble D1 + D2 form of sheep LFA-3 (sLFA-3) was expressed in Escherichia coli and the properties of the purified recombinant protein were assessed by inhibition of T-cell rosette formation. sLFA-3 inhibited rosette formation, but its activity was low, 50% inhibition occurring at 25 mu g/ml, consistent with the observed low binding avidity of fluorescein isothiocyanate (FITC)-labelled sLFA-3. sLFA-3 was made multimeric to increase its affinity, by crosslinking biotinylated sLFA-3 to streplavidin-biotinylated dextran complexes. The binding of crosslinked sLFA-3 multimers, tasted by fluorescence-activated cell sorting (FACS) analysis, was significantly increased compared to sLFA-3 monomers. Competition with monoclonal antibodies demonstrated that multimeric sLFA-3 bound to the T11(1) epitope on CD2. The multimeric form of sLFA-3 was significantly more potent than the monomer in inhibiting proliferation of human T cells in response to purified protein derivative (PPD), tetanus toroid (TT) or allogeneic cells. Multimeric sLFA-3 might, therefore, have potential as an immunotherapeutic agent to inhibit and/or anergize antigen-specific T-cell responses.
- Publisher
- BLACKWELL SCIENCE LTD
- Keywords
- FUNCTION-ASSOCIATED ANTIGEN-3; ALTERNATIVE PATHWAY; CD2; ACTIVATION; RECEPTOR; LIGAND; ADHESION; SURFACE; UNRESPONSIVENESS; RESPONSES
- Publisher's Version
- https://doi.org/10.1046/j.1365-2567.1997.00317.x
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- Refer to copyright notice on published article.
Creation Date: 1997-09-01 12:00:00