Antigen receptor engagement initiates clonal expansion and antibody secretion in B lymphocytes in response to foreign antigens. However, binding of self antigen to antigen receptors targets self-reactive B cell clones for elimination or inactivation. The antigen-triggered biochemical events and the eventual response of the cells are dependent on the simultaneous occupancy of co-stimulatory receptors. CD2 is an intercellular adhesion molecule implicated in cell activation and expressed in human T and natural killer cells as well as in mouse B lymphocytes. Mouse B cells specific for allogeneic major histocompatibility complex (MHC) class I initiate a suicide program that leads to DNA fragmentation and cell death when confronted with soluble MHC class I while undergoing clonal expansion when the antigen is present on mitomycin C-treated cells. Here we show that occupancy of CD2 in mouse B cells by the presence of either monoclonal antibody (mAb) specific for CD2, or soluble recombinant mouse CD48, its natural ligand in mouse, prevents the induction of apoptosis. Furthermore, the in vitro activation by mitomycin C-treated allogeneic cells, is abrogated in the presence of anti-CD48 mAb (OX78). These results indicate that a CD2-CD48 interaction is involved in the control of B cell activation.
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http://dx.doi.org/10.1002/eji.1830241038 | DOI Listing |
Sci Immunol
August 2022
Laboratory of Molecular Oncology, Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec H2W 1R7, Canada.
CD2 is largely described to promote T cell activation when engaged by its ligands, CD48 in mice and CD58 in humans, that are present on antigen-presenting cells (APCs). However, both CD48 and CD58 are also expressed on T cells. By generating new knockout mouse strains lacking CD2 or CD48 in the C57BL/6 background, we determined that whereas CD2 was necessary on T cells for T cell activation, its ligand CD48 was not required on APCs.
View Article and Find Full Text PDFChem Biol Drug Des
July 2013
Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA.
Targeting co-stimulatory molecules to modulate the immune response has been shown to have useful therapeutic effects for autoimmune diseases. Among the co-stimulatory molecules, CD2 and CD58 are very important in the early stages of generation of an immune response. Our goal was to utilize CD2-derived peptides to modulate protein-protein interactions between CD2 and CD58, thereby modulating the immune response.
View Article and Find Full Text PDFCytokine
December 2012
Department of Integrative Medicine and Neurobiology, National Key Lab of Medical Neurobiology, Institute of Brain Sciences, Fudan University, Shanghai, China.
Introduction: Denervation of skeletal muscles results in timely muscle-T cell cross-talk, but the mechanistic details of the orchestrated local circuits, as well as the potential regulatory link to the muscular function have not been established.
Methods: We used a combination of techniques to measure: (i) timely expression of IL-1β-ERK1/2 and IL-15-Akt signaling and (ii) cellular events controlled by IL-15-Akt signaling. Techniques included gastrocnemius strip, satellite cell culture, real time PCR, immunoprecipitation, Western blotting and subcellular fractionation.
J Biol Chem
December 2008
Programs in Molecular Pathogenesis and Structural Biology, Helen and Martin Kimmel Center for Biology and Medicine of the Skirball Institute and New York University School of Medicine, New York, New York 10016, USA.
The relationship between intermembrane spacing, adhesion efficiency, and lateral organization of adhesion receptors has not been established for any adhesion system. We have utilized the CD2 ligand CD48 with two (wild type CD48 (CD48-WT)), four (CD48-CD2), or five (CD48-CD22) Ig-like domains. CD48-WT was 10-fold more efficient in mediating adhesion than CD48-CD2 or CD48-CD22.
View Article and Find Full Text PDFProtein Sci
March 2008
Department of Chemistry, Center for Drug Design and Biotechnology, Georgia State University, Atlanta, Georgia 30303, USA.
Electrostatic interactions are important for molecular recognition processes including Ca2+-binding and cell adhesion. To understand these processes, we have successfully introduced a novel Ca2+-binding site into the non-Ca2+-dependent cell adhesion protein CD2 using our criteria that are specifically tailored to the structural and functional properties of the protein environment and charged adhesion surface. This designed site with ligand residues exclusively from the beta-sheets selectively binds to Ca2+ and Ln3+ over other mono- and divalent cations.
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