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Biotech / Medical : Biotransplant(BTRN) -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (211)	2/24/1999 1:05:00 AM
From: scaram(o)uche	Respond to of 1475

an older piece of work that I found...... Immunology 1997 Sep;92(1):39-44 A multimeric form of soluble recombinant sheep LFA-3 (CD58) inhibits human T-cell proliferation. Yamashita K, Parish CR, Warren HS, Harrison LC Kaneka Corporation, Takasago Research Laboratories, Hyogo, Japan. The rosetting 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 micrograms/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 streptavidin-biotinylated dextran complexes. The binding of crosslinked sLFA-3 multimers, tested 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 toxoid (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.

To: scaram(o)uche who wrote (211)	2/24/1999 1:13:00 AM
From: scaram(o)uche	Read Replies (1) \| Respond to of 1475

I've seen this before, but I don't think that I've ever posted it. Just stuff....... Eur J Immunol 1998 Jan;28(1):70-9 Down-modulation of CD2 delays deletion of superantigen-responsive T cells. Fortner KA, Russell JQ, Budd RC Department of Medicine, The University of Vermont College of Medicine, Burlington 05405-0068, USA. CD2 is a cell surface glycoprotein expressed on most T lymphocytes that is generally viewed as a cell adhesion molecule and, in this capacity, contributes to T cell receptor (TCR) signaling. CD2 has a relatively long cytoplasmic tail which associates with the src family tyrosine kinases, p56(lck) and p59(fyn), and could potentially signal directly. Down-modulation of CD2 on T cells has been shown to result in diminished proliferative capacity and interleukin (IL)-2 production. Furthermore, re-expression of CD2 can result in the restoration of these functions. This suggests that CD2 can influence the intensity of TCR signaling. As TCR signal intensity is pivotal to the induction of T cell apoptosis, we considered the hypothesis that the level of CD2 on the T cell surface may influence its propensity toward apoptosis. Using an anti-CD2 antibody, CD2 was down-modulated in vivo on mouse T lymphocytes without affecting the levels of surface CD3, TCR alphabeta, CD4 or CD8. Deletion of superantigen-responsive T cells was delayed in mice with down-modulated CD2 following the administration of staphylococcal enterotoxin B (SEB). This was paralleled by diminished apoptosis of SEB-responsive cells. The findings suggest a model whereby the level of CD2 expression influences the intensity of TCR signaling and the ability to undergo apoptosis.