CD23/CD21 interaction is required for presentation of soluble protein antigen by lymphoblastoid B cell lines to specific CD4⁺ T cell clones

Abstract

Previous studies have documented a role for membrane-bound CD23 (the low affinity Fc epsilon RII) in presentation of alloantigens by B cells. The aim of the present study was to examine the involvement of cell surface CD23 in presentation of more conventional soluble protein antigens to T cells. We show that antibodies to CD23 and to its lymphocyte-associated second ligand, CD21, inhibit presentation of the cow's milk allergen casein, by autologous CD23+CD21+ B-EBV cell lines to casein-specific HLA-DP-restricted CD4+ T cell clones obtained from patients with either reaginic or enterophatic forms of cow's milk protein intolerance. Maximal inhibition was achieved when the antibodies were added at the initiation of the culture. The absence of specific inhibition by an anti-DR alpha monoclonal antibody (mAb) argues against a steric hindrance phenomenon impeding access of the T cell receptor to major histocompatibility complex class II molecules. Rather, anti-CD23 and anti-CD21 mAb-induced inhibition of antigen presentation seems to affect at least partly, heterotypic conjugate formation through CD23/CD21 interaction. Double immunofluorescence labeling of the T cell clones and antibody inhibition of T/B conjugate formation shows that functional CD23 and CD21 molecules are induced on T cells following contact with B-EBV cell lines. Taken together, these data indicate that CD23/CD21 interactions between T and B cells are required for presentation of soluble protein antigens by B-EBV cell lines to specific CD4+ T cells. The potential implications of these findings for allergen-specific T cell activation are discussed.

Characterization of Human Complement Receptor Type 2 (CR2/CD21) as a Receptor for IFN-α: A Potential Role in Systemic Lupus Erythematosus

“…CD23 is an immunoregulatory protein found both on cell membranes and as a soluble protein. CD23 interacts with CR2 to increase production of IgE in the presence of IL-4 (3), rescue germinal-center B cells from apoptosis (24), provide T cell-activating signals by B cell APCs (25), and promote T-B cell adhesion (26).…”

“…CR2 SCR1-15 was dialyzed overnight at 4°C against 50 mM PBS with differing pH (5.5, 6.0, 6.5, 7.0, 7.5, and 8.0) and in a separate experiment 50 mM PBS containing differing NaCl concentrations (25,50,75, 100, 125, and 150 mM). Then, 5 g/ml human rhIFN-␣ (5 ϫ 10 6 U/ml) (PBL Biomedical Laboratories) was immobilized on 96-well ELISA plates (Costar) in bicarbonate buffer (pH 9.0) overnight at 4°C.…”

Expression of CD21 and CD23 during Human Fetal Development

“…CD23 and CD21 have biologic effects additional to those described for IgE production, including B-cell proliferation, antigen presentation, and the response to soluble antigen, T-B cell adhesion, and apoptosis (33)(34)(35)(36)(37). Further functional studies are necessary to elaborate whether CD21 and/or CD23 expression contribute to any of these functions in the neonate.…”

Epitope Mapping Using the X-Ray Crystallographic Structure of Complement Receptor Type 2 (CR2)/CD21: Identification of a Highly Inhibitory Monoclonal Antibody That Directly Recognizes the CR2-C3d Interface

“…CR2 can also mediate uptake and presentation of Ags to specific T cells (17,18). As a receptor for CD23, CR2 promotes B cell class switching and production of IgE isotype Abs (9), rescues germinal center B cells from apoptosis (19), and enhances T-B cell-cell adhesive interactions (20).…”