CDB25:0003274 CD2 — CD58
Experimentally validated in Human, Zebrafish; Orthology-inferred in Human, Macaque, Pig, Dog, Cow, Chimp, Horse, Sheep
Title
Journal:; Year Published:
Abstract
Costimulatory Function of Cd58/Cd2 Interaction in Adaptive Humoral Immunity in a Zebrafish Model.
Frontiers in immunology, 2018; PubMed, Danio rerio cd2 — Danio rerio cd58
ABSTRACT: CD58 and CD2 have long been known as a pair of reciprocal adhesion molecules involved in the immune modulations of CD8+ T and NK-mediated cellular immunity in humans and several other mammals. However, the functional roles of CD58 and CD2 in CD4+ T-mediated adaptive humoral immunity remain poorly defined. Moreover, the current functional observations of CD58 and CD2 were mainly acquired from in vitro assays, and in vivo investigation is greatly limited due to the absence of a Cd58 homology in murine models. In this study, we identified cd58 and cd2 homologs from the model species zebrafish (Danio rerio). These two molecules share conserved structural features to their mammalian counterparts. Functionally, cd58 and cd2 were significantly upregulated on antigen-presenting cells and Cd4+ T cells upon antigen stimulation. Blockade or knockdown of Cd58 and Cd2 dramatically impaired the activation of antigen-specific Cd4+ T and mIgM+ B cells, followed by the inhibition of antibody production and host defense against bacterial infections. These results indicate that CD58/CD2 interaction was required for the full activation of CD4+ T-mediated adaptive humoral immunity. The interaction of Cd58 with Cd2 was confirmed by co-immunoprecipitation and functional competitive assays by introducing a soluble Cd2 protein. This study highlights a new costimulatory mechanism underlying the regulatory network of adaptive immunity and makes zebrafish an attractive model organism for the investigation of CD58/CD2-mediated immunology and disorders. It also provides a cross-species understanding of the evolutionary history of costimulatory signals from fish to mammals as a whole.
Human cell-adhesion molecule CD2 binds CD58 (LFA-3) with a very low affinity and an extremely fast dissociation rate but does not bind CD48 or CD59.
Biochemistry, 1994; PubMed, Homo sapiens CD2 — Homo sapiens CD58
ABSTRACT: CD2 is a T lymphocyte cell-adhesion molecule (CAM) belonging to the immunoglobulin superfamily (IgSF) which mediates transient adhesion of T cells to antigen-presenting cells and target cells. Reported ligands for human CD2 include the structurally-related IgSF CAMs CD58 (LFA-3) and CD48 as well as, more controversially, the unrelated cell-surface glycoprotein CD59. Using surface plasmon resonance technology, which avoids several pitfalls of conventional binding assays, we recently reported that rat CD2 binds rat CD48 with a very low affinity (Kd 60-90 microM) and dissociates rapidly (koff > or = 6 s-1) [van der Merwe, P. A., Brown, M. H., Davis, S. J., & Barclay, A. N. (1993) EMBO J. 12, 4945-4954]. In contrast, a study using conventional equilibrium binding methods reported a much higher affinity (Kd 0.4 microM) for human CD2 binding CD58 which suggested that the weak binding of rat CD2 to CD48 may not represent a typical CAM interaction. In the present study we have used surface plasmon resonance to obtain definitive affinity and kinetic data on the interactions of a soluble, recombinant form of human CD2 with soluble forms of CD58, CD48, and CD59. Binding of CD2 to CD58 was readily detected but we were unable to detect any direct interaction between CD2 and either CD59 or CD48 under conditions in which very low affinity interactions (Kd approximately 0.5 mM) would have been detected. In contrast to previous reports we found that human CD2 bound CD58 with a very low affinity (Kd 9-22 microM) and dissociated with an extremely fast dissociation rate constant (koff > or = 4 s-1). The association rate constant (kon) could not be measured directly but was calculated to be > or = 400,000 M-1s-1. Taken together, these results provide conclusive evidence that CAM interactions can have very low affinities and extremely fast dissociation rate constants.