Inhibition of T cell activation and adhesion functions by soluble CD2 protein.
The CD2 (T11) molecule belongs to a family of cell-surface glycoproteins that function as adhesion molecules in the immune system. Human CD2 is found exclusively on cells of the T lineage: peripheral T lymphocytes, NK cells, and thymocytes. CD2 binds specifically to the surface glycoprotein LFA-3. CD2/LFA-3 adhesion is the basis for the formation of rosettes between T cells and sheep erythrocytes (SRBC) which bear the sheep homologue of LFA-3. More importantly, CD2/LFA-3 adhesion functions in the immune system to augment T cell activation; it initiates conjugate formation between participating T cells and antigen-presenting cells (APC). We investigated the effects of soluble forms of CD2 (sCD2), produced in either baculovirus or CHO expression systems, on the rosetting of T cells with SRBC and on the activation of T cells by antigen plus major histocompatibility complex (MHC) molecules. Rosette formation between T cells and SRBC was completely inhibited by as little as 1 microM sCD2. Furthermore, sCD2 effectively inhibited (at micromolar concentrations) the T cell proliferative response to recall antigens including rubella, tetanus toxoid, and herpes simplex virus (HSV-1), as well as alloantigens in a mixed lymphocyte culture. These findings are consistent with the notion that the CD2/LFA-3 interaction augments antigen-specific T cell functions. The use of a CD2 "decoy" molecule rather than anti-CD2 or anti-LFA-3 antibodies to block the CD2/LFA-3 interaction rules out secondary antibody effects, via the Fc portion, as the basis for inhibition of T cell activation and directly stresses the importance of this adhesion interaction in T cell responses.
Rabin
E M
EM
PROCEPT, Inc., Cambridge, Massachusetts 02139.
Gordon
K
K
Knoppers
M H
MH
Luther
M A
MA
Neidhardt
E A
EA
Flynn
J F
JF
Sardonini
C A
CA
Sampo
T M
TM
Concino
M F
MF
Recny
M A
MA
D015703:Antigens, CD / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000737:chemistry / Q000502:physiology*; D000956:Antigens, Viral / Q000276:immunology; D018801:CD2 Antigens; D018968:CD58 Antigens; D002448:Cell Adhesion / Q000187:drug effects*; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000502:physiology; D011971:Receptors, Immunologic / Q000737:chemistry / Q000502:physiology*; D011994:Recombinant Proteins; D012397:Rosette Formation; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D018801:CD2 Antigens; D018968:CD58 Antigens; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D013745:Tetanus Toxoid