Disease relevance of CD48

• While soluble CD48 was detected in the plasma of healthy individuals (median = 29 ng/ml; range, 15-48 ng/ml), elevated levels were detected in some patients with lymphoproliferative disease (median = 41 ng/ml; range, 9-213 ng/ml, arthritis (median = 42 ng/ml; range, 13-67 ng/ml), and acute EBV infection (174 ng/ml) [1].
• Detection of a soluble form of the leukocyte surface antigen CD48 in plasma and its elevation in patients with lymphoid leukemias and arthritis [1].
• We report here that two such tumors, the Ag104A sarcoma and the K1735-M2 melanoma, become immunogenic after transfection of the genes encoding murine B7-1 together with CD48, which is the natural ligand for CD2 [2].
• Cholesterol-dependent clustering of IL-2Ralpha and its colocalization with HLA and CD48 on T lymphoma cells suggest their functional association with lipid rafts [3].
• In most leukemias, both CD48 and NTBA were down-regulated [4].

High impact information on CD48

• Engagement of receptor 2B4 by CD48 on insect cells induced weak polarization and no degranulation [5].
• This effect strongly correlated with expression of CD48 on tumor cells, the ligand of 2B4, a SLAM-related receptor expressed in NK cells [6].
• In the case of autologous or allogeneic (HLA class I(+)) EBV(+) lymphoblastoid cell lines, restoration of lysis was achieved only by the simultaneous disruption of 2B4-CD48 and NK receptor-HLA class I interactions [7].
• The finding of an additional ligand for CD48 provides an explanation for distinct functional effects observed on perturbing CD2 and CD48 with mAbs or by genetic manipulation [8].
• Given the importance of the CD2-CD48 interaction in the murine system and CD2-CD58 interaction in humans, it would appear that there has been a divergence of functional CD2 ligands during the evolution of humans and mice [9].

Chemical compound and disease context of CD48

• Biochemical fractionation and confocal imaging of HIV-1 receptor distribution in live cells demonstrated that CD4, CCR5, and CXCR4 colocalized with raft-resident markers, ganglioside GM1, and glycosylphosphatidylinositol-anchored CD48 [10].
• CD48, a mannose containing GPI (glycosylphosphatidylinositol)-linked molecule was found to be the receptor of FimH-expressing E. coli in mouse mast cells [11].
• Operons coding for the enzyme arsenite oxidase have been detected in the genomes from Archaea and Bacteria by Blast searches using the amino acid sequences of the respective enzyme characterized in two different beta-proteobacteria as templates [12].

Biological context of CD48

• Chromosome localization studies mapped the HLy9-beta gene to chromosome 1q24, where other members of this Ig superfamily (CD48 and HumLy9) have been mapped [13].
• CD48 is a member of the Ig superfamily with a high degree of sequence homology to CD58 (LFA-3) [14].
• We further show that the cell surface proteoglycan CD44 plays an auxiliary role in the binding of epithelial cells to CD48 and that this interaction involves the glycosaminoglycan binding site of CD44 [14].
• Topology of the CD2-CD48 cell-adhesion molecule complex: implications for antigen recognition by T cells [15].
• These results show that rat CD48 binds CD2 on its NH2-terminal IgSF domain with a low affinity and that binding is independent of glycosylation [16].

Anatomical context of CD48

• 2B4, the natural killer and T cell immunoglobulin superfamily surface protein, is a ligand for CD48 [8].
• Two of three tested patients with PNH and 1 of 12 patients with AA had a defect in the CD48 lymphocyte population [17].
• Characterization of the Epstein-Barr virus-inducible gene encoding the human leukocyte adhesion and activation antigen BLAST-1 (CD48) [18].
• Using soluble receptor fusion proteins and SRR-transfected cells, we show that 2B4 does not bind to any other SRR expressed on NK cells, but only interacts with CD48 [19].
• A ligand for human CD48 on epithelial cells [14].

Associations of CD48 with chemical compounds

• To determine the structural basis for 2B4/CD48 interaction, selected amino acid residues in the V domain of the human 2B4 (h2B4) were mutated to alanine by site-directed mutagenesis [20].
• 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] [21].
• In the course of these studies, we have isolated a human cDNA coding for the glycosyl-phosphatidylinositol-linked (GPI) membrane glycoprotein CD48 (TCT-1, Blast-1) [22].
• Functional role played by the glycosylphosphatidylinositol anchor glycan of CD48 in interleukin-18-induced interferon-gamma production [23].
• CD48 is an allergen and IL-3-induced activation molecule on eosinophils [24].

Physical interactions of CD48

• We identified amino acid residues in the extracellular domain of h2B4 that are involved in interacting with CD48 [20].
• In mice, the CD48 molecule can bind to CD2 [25].
• CD48 via both the peptide portion and GPI glycan triggers the binding to IL-18Rbeta, and the IL-18.IL-18Ralpha.CD48.IL-18Rbeta complex induces cellular signaling [23].

Regulatory relationships of CD48

• Instead, 2B4 is activated by binding to CD48, a GPI-anchored surface molecule that is widely expressed in the hemopoietic system [19].
• CD40 induced earlier changes in the protein phosphorylation than CD48 did [26].
• To determine which GPI-anchored glycoprotein is involved in the complex of IL-18 and IL-18Ralpha, IL-18Ralpha of IL-18-stimulated KG-1 cells was immunoprecipitated together with CD48 by anti-IL-18Ralpha antibody [23].
• Combined application of CD2 and CD48 mAb did not enhance immunosuppression induced by CD2 mAb alone [27].
• These results indicate that a CD2-CD48 interaction is involved in the control of B cell activation [28].

Other interactions of CD48

• We have recently identified CD48 as the high affinity counterreceptor for 2B4 in both mice and humans [29].
• Coexpression of CD58 or CD48 with intercellular adhesion molecule 1 on target cells enhances adhesion of resting NK cells [30].
• It is a 365-amino acid protein that belongs to the immunoglobulin-like superfamily with closest homology to murine 2B4, and human CD84 and CD48 [31].
• In this model of B cell differentiation only the AM CD58 depend on the presence of T cells while CD48 and CD80 help was found to be T cell independent [32].
• The results of the present report, together with our previous functional studies, may have implications for the role of CD2 and CD48 in murine T-cell activation [33].

Analytical, diagnostic and therapeutic context of CD48

• The results of immunofluorescence and immunoprecipitation experiments in which this reagent was used identify the 2B4 molecule as a novel counter-receptor of CD48 [25].
• Recently, 2B4 was shown to bind CD48 by molecular binding assays and surface plasmon resonance [34].
• Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48 [31].
• The CD48 binding surface was identified by monitoring perturbations in the line widths and chemical shifts of cross peaks in the HSQC spectrum of CD2d1 during titrations with a soluble form of CD48 expressed in Chinese hamster ovary cells [35].
• Flow cytometric analysis revealed a moderate down modulation of CD48, CD3 and CD8 after treatment with anti-CD48 [36].

References