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At least 19 recordsLinked to original sources
PubMed1991

New monoclonal antibodies in CD44 and CD58: their use to quantify CD44 and CD58 on normal human erythrocytes and to compare the distribution of CD44 and CD58 in human tissues.

The cell-surface glycoproteins CD44 and CD58 are involved in cell adhesion reactions. In this paper 12 monoclonal antibodies in CD44 and two in CD58 are described. Competitive binding assays using CD44 antibodies identified three distinct epitope groups. Antibodies in Group 1 and, with one exception (BRIC 214), antibodies in group 2, but not antibodies in Group 3, recognized epitopes that are sensitive to reduction and to trypsin or chymotrypsin treatment of intact erythrocytes, and so these epitopes probably reside on the N-terminal disulphide-bonded domain of CD44. Antibodies in CD44 did not inhibit the binding of CD58 antibodies to erythrocytes or vice versa. Quantitative binding studies using radioiodinated IgG measured 1888-5592 copies of CD44 and 1772-3290 copies of CD58 on normal erythrocytes. Similar measurements with radioiodinated Fab fragments gave values of 6508-10,450 (CD44) and 3457-7622 (CD58). Immunocytochemical studies indicated that CD44 is much more widely expressed in non-haemopoietic tissues than CD58. Comparison with previously described CD44 antibodies suggests that antibodies in our Group 1 encompass Hermes 2 and that those in Group 2 encompass Hermes 1. All the CD44 antibodies gave weakened reactions with Lu(a-b-) erythrocytes of the In(Lu) type by one or more methods. BRIC 214 and antibodies in epitope Group 3 were used to demonstrate that CD44 on these variant cells gives membrane-bound trypsin and chymotrypsin cleavage fragments of similar molecular weight to those obtained with normal erythrocytes.

Antibodies, Monoclonal↗
PubMed1992

The lymphoma transmembrane glycoprotein GP85 (CD44) is a novel guanine nucleotide-binding protein which regulates GP85 (CD44)-ankyrin interaction.

In this study, we have used photoaffinity labeling by [32P]azido-GTP as well as [32P]ADP-ribosylation by pertussis toxin (PT) and cholera toxin (CT) to identify GTP-binding proteins associated with mouse T-lymphoma plasma membranes. Our results indicate that GP85 (CD44) can be photoaffinity labeled by [32P] azido-GTP and [32P]ADP-ribosylated by both PT and CT. Using purified GP85 (CD44) obtained by Triton X-100 extraction, wheat germ agglutinin-Sepharose, and anti-GP85 (CD44) antibody affinity chromatographies, we have further characterized GP85 (CD44) as a GTP-binding protein. GP85 (CD44) is found to bind guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) in a time- and dose-dependent manner with a dissociation constant of 0.83 nM. Importantly, GP85 (CD44) appears to display a GTPase activity which hydrolyzes [gamma-32P]GTP at a rate of 0.011 mol of Pi released/mol of GP85 (CD44)/min. This GTPase activity can be readily inhibited by PT- or CT-mediated ribosylation of GP85 (CD44). Most interestingly, GTP binding significantly enhances the interaction of purified GP85 (CD44) with ankyrin, whereas ADP-ribosylation of GP85 (CD44) by PT or CT inhibits the GTP-induced increase in ankyrin binding to GP85 (CD44). In addition to GP85 (CD44) being the first reported transmembrane GTP-binding protein, these results suggest that GTP plays an important role in promoting the interaction between GP85 (CD44) and its underlying membrane cytoskeleton through ankyrin.

Adenosine Diphosphate Ribose↗
PubMed1992

Shedding of the CD44 adhesion molecule from leukocytes induced by anti-CD44 monoclonal antibody simulating the effect of a natural receptor ligand.

The CD44 adhesion molecule, playing an important role in leukocyte extravasation, was down-regulated by PMA and ionomycin on granulocytes and by an immobilized or soluble anti-CD44 mAb both on granulocytes and lymphocytes. Soluble labeled CD44 molecules of lower apparent molecular mass as compared to their membrane counterparts were isolated from culture supernatants of stimulated surface iodinated cells. Shedding rather than internalization is the mechanism found to be responsible for the loss of CD44 from the cell surface. The size of the soluble CD44 shed from the cells stimulated in vitro corresponds to soluble CD44 isolated from human serum. These data suggest that shedding, induced by anti-CD44 antibody simulating the effect of a natural CD44 ligand, is an important regulatory mechanism controlling surface CD44 expression on leukocytes in vivo.

Antibodies, Monoclonal↗
PubMed1992

Schistosoma mansoni eggs induce antigen-responsive CD44-hi T helper 2 cells and IL-4-secreting CD44-lo cells. Potential for T helper 2 subset differentiation is evident at the precursor level.

Schistosoma mansoni eggs are potent inducers of biased Th2-like immune responses. Using a model system where mice are immunized with isolated schistosome eggs, we demonstrate that CD44 expression, up-regulation of which has been linked to Th cell development, is increased on Th2 cells. We also investigate the functional properties of CD44-lo Th cells recovered from the overtly Th2 environment constituted by lymph nodes draining sites of egg deposition. Production of high levels of IL-4, IL-5, and IL-10 by Th cells responding to egg Ag is shown to be the property of a subpopulation expressing CD44-hi. This population of Th cells cosegregates with a blasting subpopulation expressing more IL-4R (but similar amounts of IL-2R) than Th cells from normal mice. These results indicate that mature Th2 cells responding to schistosome eggs are CD44-hi and suggest that they use IL-4 as a growth factor. In contrast, CD44-lo cells sorted from lymph node populations responding to eggs are able to produce small amounts of IL-4 and IL-2, but no IL-5 or IL-10. This is surprising, because low expression of CD44 is considered a characteristic of Th cell naivite and concomitant ability to produce only IL-2. Thus, in lymph nodes responding to schistosome eggs, potential for Th2 subset differentiation is evident within the CD44-lo precursor Th subpopulation.

Animals↗
PubMed1992

The complex CD44 transcriptional unit; alternative splicing of three internal exons generates the epithelial form of CD44.

We have utilized the polymerase chain reaction (PCR) to isolate a 3.5 kilobase pair (kb) genomic fragment that encodes the additional extracellular domain unique to the epithelial isoform of CD44 (CD44E). Nucleotide sequence was determined for this complete region and sequence comparison to our previously determined CD44R1 and CD44R2 cDNA sequences revealed the R region to be comprised of three exons of 102 bp, 90 bp, and 204 bp. Northern blot analysis of CD44 expressing cell lines confirmed the presence of CD44R1 transcripts and indicates that the epithelial domain may be inserted through alternative splicing into all CD44 transcript classes. Southern blot analysis of the CD44E genomic fragments is consistent with a single copy per human haploid genome. The data presented here further supports our model of the human CD44 transcriptional unit as a single gene complex that utilizes an invariant 5' initiation site, alternative internal and 3' end splicing, and multiple poly (A) sites to generate through RNA processing a diverse number of human CD44 isoforms.

Amino Acid Sequence↗
PubMed1990

Homotypic cell aggregation induced by anti-CD44(Pgp-1) monoclonal antibodies and related to CD44(Pgp-1) expression.

The present study shows that a mAb (H4C4) developed against human peripheral blood adherent cells has the unusual property of inducing in vitro homotypic aggregation of several types of hemopoietic cells and cell lines. The Ag recognized by mAb H4C4 is a 85-kDa glycoprotein that corresponds to the human Ag CD44 (equivalent to murine Pgp-1), as determined by protein purification, immunologic cross-reactivity studies, and tryptic fragment sequencing. In addition to H4C4, other mAb directed against some, but not all, epitopes of CD44(Pgp-1) were capable of inducing cell aggregation. This process was temperature sensitive and was almost totally abrogated by cytochalasin B but was unaffected by sodium azide, colchicine, EGTA, trifluoperazine, or staurosporin. A role for CD44 (Pgp-1) in cell-to-cell adhesion was further indicated by an inverse relationship observed between spontaneous aggregation of some hemopoietic cell lines and cell-surface expression of CD44(Pgp-1). These observations provide evidence for a fundamental role of CD44(Pgp-1) in cellular aggregation phenomena with an involvement of the cytoskeleton.

Amino Acid Sequence↗
PubMed1992

Requirements for hyaluronic acid binding by CD44: a role for the cytoplasmic domain and activation by antibody.

The CD44-negative T lymphoma AKR1 (CD44.2 genotype) was transfected with a CD44.1 cDNA. The intact cDNA conferred on the transfected cells the ability to bind hyaluronic acid (HA) both from solution and immobilized on culture plates. It also conferred a CD44-dependent and hyaluronidase-sensitive increase in adhesion to a lymph node endothelial cell line. A mutant cDNA which codes for a CD44 molecule lacking most of the cytoplasmic domain of CD44 was also transfected into AKR1, and cell sorting was used to select transfectants expressing levels of cell surface CD44 expression comparable with the line transfected with the wild-type CD44 cDNA. The cells transfected with the mutant construct bound fluoresceinated HA from solution very poorly, but did adhere to immobilized HA, though less well than cells transfected with the wild-type construct. This result indicates that the cytoplasmic domain of CD44 is necessary for binding of HA from solution but is not required for binding to immobilized HA, although it may contribute to adhesion following ligand recognition. A monoclonal antibody (mAb), IRAWB 14, which reacts with CD44 on all CD44+ cells dramatically induced HA binding by some CD44+ cell lines that did not constitutively bind HA. The transfectant expressing a CD44 molecule with a truncated cytoplasmic domain could be induced by this antibody to bind fluoresceinated-HA from solution. Splenic T cells did not bind fluoresceinated HA constitutively. In the presence of the IRAWB 14 mAb, virtually all CD44+ splenic T cells bound HA. Induction was immediate and occurred equally well at room temperature and at 4 degrees C, indicating that the new HA-binding activity was due to preexistent CD44 molecules. These results are compatible with an antibody-induced activation of CD44 by either a conformational change in the CD44 molecule or a change in the distribution of CD44 molecules on the cell surface.

Animals↗
PubMed1990

Antibodies against the CD44 p80, lymphocyte homing receptor molecule augment human peripheral blood T cell activation.

The CD44 inhibitor Lutheran [In(Lu)]-related p80 molecule has recently been shown to be identical to the Hermes-1 lymphocyte homing receptor and to the human Pgp-1 molecule. We have determined the effect of addition of CD44 antibodies to in vitro activation assays of PBMC. CD44 antibodies did not induce PBMC proliferation alone, but markedly enhanced PBMC proliferation induced by a mitogenic CD2 antibody pair or by CD3 antibody. CD44 antibody addition had no effect upon PBMC activation induced by PHA or tetanus toxoid. CD44 antibody enhancement of CD2 antibody-induced T cell activation was specific for mature T cells as thymocytes could not be activated in the presence of combinations of CD2 and CD44 antibodies. CD44 antibody enhancement of CD2-mediated T cell triggering occurred if CD44 antibody was placed either on monocytes or on T cells. In experiments with purified monocyte and T cell suspensions, CD44 antibodies A3D8 and A1G3 augmented CD2-mediated T cell activation by three mechanisms. First, CD44 antibody binding to monocytes induced monocyte IL-1 release, second, CD44 antibodies enhanced the adhesion of T cells and monocytes in CD2 antibody-stimulated cultures, and third, CD44 antibodies augmented T cell IL-2 production in response to CD2 antibodies. Thus, ligand binding to CD44 molecules on T cells and monocytes may regulate numerous events on both cell types that are important for T cell activation. Given that recent data suggest that the CD44 molecule may bind to specific ligands on endothelial cells (vascular addressin) and within the extracellular matrix (collagen, fibronectin), these data raise the possibility that binding of T cells to endothelial cells or extracellular matrix proteins may induce or up-regulate T cell activation in inflammatory sites.

Antigen-Presenting Cells↗
PubMed2026

CD44 gene rs9666607 polymorphism is associated with papillary thyroid carcinoma and interacts with CREB3L1.

BACKGROUND: The incidence of papillary thyroid carcinoma (PTC) has been rising. CD44 is involved in cell adhesion and migration, but the role of its genetic variation in PTC remains unclear. METHODS: This study aimed to investigate the association of CD44 gene polymorphisms with PTC and to examine the interaction between CD44 and CREB3L1. This study enrolled 354 patients with PTC, and the genotype distribution of the CD44 polymorphism (rs9666607) was analyzed. Key PTC genes were screened using the Gene Expression Omnibus (GEO) database (GSE33630). Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on these key genes. CD44 expression was validated using TCGA database, ELISA, qRTPCR, Western blot, and IHC in patient tissues, PTC mouse model, and human cell lines. The direct interactive molecules were screened through a bioinformatics method. RESULTS: The GSE33630 dataset identified a total of 124 upregulated and 85 downregulated differentially expressed genes. Enrichment analysis revealed 12 key PTC genes, including CD44. TCGA database validation revealed that CD44 was significantly overexpressed in PTC patients. The rs9666607‑A allele was associated with an increased risk of PTC and lymph node metastasis under a dominant model. CD44 mRNA and protein levels were significantly higher in PTC tissues versus adjacent tissue and further elevated in metastatic cases. Bioinformatic analysis predicted CD44 interaction with the transcription factor CREB3L1, and this was confirmed by molecular docking. CREB3L1 expression was synchronously upregulated with CD44 in PTC. CONCLUSION: CD44 polymorphisms, particularly the rs9666607-A allele, are significantly associated with PTC risk and metastasis in the studied population. CD44 is overexpressed in PTC, and its interaction with CREB3L1 suggests a potential novel interaction in PTC pathogenesis.

Hyaluronan Receptors↗
PubMed1991

Measurement of an adhesion molecule as an indicator of inflammatory disease activity. Up-regulation of the receptor for hyaluronate (CD44) in rheumatoid arthritis.

The hyaluronate receptor (CD44) molecule is a multifunctional cell surface protein involved in T cell activation, monocyte cytokine release, fibroblast locomotion, and lymphocyte binding to high endothelial venules. To study the roles CD44 molecules play in inflammatory synovitis, we measured expression of CD44 in inflamed and noninflamed synovial fluid and tissue, using indirect immunofluorescence assays on tissue sections and quantitative Western blot analysis. The ability of purified CD44 protein to modulate T cell responses was tested in T cell activation assays in which CD44-containing liposomes were added in vitro. CD44 was widely expressed on many synovial cell types, and synovial tissue from rheumatoid arthritis (RA) patients contained 3.5 times more CD44 than tissue from osteoarthritis patients and 10.7 times more than tissue from patients with joint trauma. The level of soluble CD44 in RA synovial fluid was elevated only in fluids with low cell counts (less than or equal to 7,000/mm3), and not in RA synovial fluid with higher cell counts. Soluble purified CD44 protein in liposomes partially suppressed T cell activation in vitro. These data demonstrate that CD44 is up-regulated on many synovial cell types in patients with RA, and that the level of CD44 present in synovial tissue is related to the degree of synovial inflammation. Determination of ways to inhibit the proinflammatory functions of immune cell membrane CD44 molecules may provide new therapeutic modalities for RA.

Adult↗
PubMed1990

Confirmation by peptide sequence and co-expression on various cell types of the identity of CD44 and P85 glycoprotein.

The p85 glycoprotein expressed on a variety of human cell types including astrocytes and lymphocytes has not been associated with the CD44 cluster. The recent demonstration that Hermes, a glycoprotein implicated in the adhesion of lymphocytes to endothelium, belongs to the CD44 cluster raises interesting questions concerning the role of this molecule on astrocytes and on non-lymphoid cells. To obtain confirmation of the identity of p85 glycoprotein and CD44, p85 glycoprotein was purified from B-chronic lymphocytic leukemia cells by affinity to monolonal 50B4-IgG and electrophoretic elution, digested with trypsin or CNBr and fractionated by reversed-phase HPLC. The sequences of three peptides were obtained which could be aligned with the amino acid sequence deduced from the CD44 cDNA at residues 49-54, 59-66 and 309-323. These constitute the first reported peptide sequences for antigens of the CD44 cluster and confirm that p85 glycoprotein is indeed the product of the CD44 gene. Since two different cDNA clones encoding molecules with cytoplasmic tails of 72 and 5 amino acids have been isolated, the isolation of peptide 309-323 confirms the existence of a processed protein with the longer cytoplasmic domain. Using a cDNA probe, we have characterized the expression of CD44 in several normal and malignant cell types. The level of CD44 mRNA was correlated with the surface expression of CD44 antigens (50B4) in several leukemic cell lines, in astrocytoma lines and in normal granulocytes. Negative cells included the Y79 retinoblastoma line, the NALM-6 leukemic line and endothelial cells. Identical mRNA species of 5.0, 2.3 and 1.7 kb were present in all CD44-positive samples, including normal granulocytes, astrocytoma, melanoma and leukemia cell lines and leukemic cells from patients. The highest level of expression of CD44 was observed on astrocytoma lines and on acute lymphoblastic leukemia cells of immature phenotype. The presence of high levels of CD44 on malignant cells could increase the ability of these cells to adhere to matrix proteins and/or to interact with endothelium, thus potentially altering their capacity for invasiveness and metastasis.

Amino Acid Sequence↗
PubMed1991

Variations in the cytoskeletal interaction and posttranslational modification of the CD44 homing receptor in macrophages.

Murine CD44 is a cell surface glycoprotein that is thought to play a role in leukocyte migration. We studied the structure and expression of CD44 on two populations of macrophages: those that reside in the peritoneum of unprimed mice, and those that have been elicited to migrate into the peritoneum by the intraperitoneal injection of agents that cause localized inflammatory responses. Our studies reveal structural variations in both the extracellular and intracellular domains of CD44 expressed by these two macrophage populations. The form of CD44 in elicited macrophages has an apparent molecular mass that is approximately 5 kD greater and more heterogenous than that in resident macrophages. This structural changes is posttranslational, extracellular, and apparently reflects increases in N-linked glycosylation. It is also specific for CD44 and does not occur with several other glycoproteins examined. This novel regulation of glycosylation may play an important role in the ability of CD44 to bind to different substrates, particularly lectin-like ligands. In addition, we demonstrate that CD44 in resident macrophages is divided into two pools, one containing nonphosphorylated, cytoskeletally associated CD44, and one containing phosphorylated, unassociated CD44. In contrast, CD44 on the surface of elicited macrophages does not associate with the cytoskeleton. The attachment of CD44 to the cytoskeleton involves either direct or indirect association with actin. The regulated association of CD44 with the cytoskeleton suggests that it may influence or be influenced by macrophage mobility.

Animals↗
PubMed1991

Molecular cloning of CD44R1 and CD44R2, two novel isoforms of the human CD44 lymphocyte "homing" receptor expressed by hemopoietic cells.

In addition to the 85-95 kD CD44 species found on most hemopoietic cell types, the human myelomonocytic cell line KG1a expresses proteins of approximately 115 kD and 130 kD that react with monoclonal antibodies belonging to CD44. The possibility that these higher molecular weight species may represent novel CD44 isoforms containing additional protein sequence was investigated. CD44 cDNA clones were isolated from a plasmid-based expression library prepared from KG1a mRNA. One of the three clones obtained (clone 2.3) was found to encode a CD44 molecule of approximately 130 kD in transfected COS cells. Sequences analysis indicated that the molecule encoded by this cDNA clone, designated CD44R1, was essentially identical to CD44 except for the presence of an additional 132 amino acids inserted into the extracellular domain. This inserted region is rich in serine and threonine residues that may serve as sites of O-linked glycosylation, and contains a potential site of N-linked glycosylation and a potential site of chondroitin sulphate attachment. PCR analysis using primers that flank the inserted region present within CD44R1 identified an additional CD44 isoform, designated CD44R2, that contains only the last 69 amino acids present within the unique region of CD44R1. Peripheral blood mononuclear cells and granulocytes from normal individuals and patients with chronic myelogenous leukemia, polycythemia vera, or acute myelomonocytic leukemia, express both CD44R1 and CD44R2. In contrast, CD44R1 and CD44R2 appear to be differentially expressed in various CD44-positive cell lines. Thus KG1a, and the Epstein-Barr Virus-transformed B cell lines WalkDR4 and Way-1 express both CD44 and the CD44 isoforms CD44R1 and CD44R2, while the myeloid cell lines HL60 and U937 express high levels of CD44, but only very low levels of CD44R1 and CD44R2. The CD44-negative cell lines DHL-4, DHL-10, Jurkat, and K562 are also negative for CD44R1 and CD44R2.

Amino Acid Sequence↗
PubMed1992

Molecular isoforms of murine CD44 and evidence that the membrane proximal domain is not critical for hyaluronate recognition.

We previously found that the CD44 glycoprotein on some lymphocytes can mediate adhesion to hyaluronate (HA) bearing cells. However, many questions remain about the molecular heterogeneity of CD44 and mechanisms which control its recognition of this ligand. In vitro mutagenesis and DNA sequencing have now been used to investigate the importance of the membrane proximal region of murine CD44 for recognition of soluble or cell surface HA. CD44 with an 83 amino acid deletion in this region mediated binding to soluble ligand and the apparent avidity increased markedly in the presence of a particular antibody to CD44, IRAWB14. The shortened CD44 was however inefficient in mediating adhesion of transfected cells to HA immobilized on cell surfaces. Four new murine isoforms of CD44 were isolated from a carcinoma line by use of the polymerase chain reaction. Only two of them correspond to ones recently discovered in rat and human cells. The longest variant nearly doubled the length of the extracellular portion of the molecule and introduced an additional 20 potential sites for glycosylation. When expressed on T lymphoma cells, all four of the new murine CD44 isoforms were capable of mediating adhesion to HA bearing cells. This result contrasts with a report that a related human CD44 isoform lacks this ability when expressed on B lineage lymphoma cells. The new murine isoforms also conferred the ability to recognize soluble HA and were very responsive to the IRAWB14 antibody. A brief survey of normal murine cell lines and tissues revealed that the hemopoietic isoform was the most abundant species. These findings indicate that the NH2-terminal portion of CD44 is sufficient for HA recognition and that this function is not necessarily abrogated by variations which occur in the membrane proximal domain. They add to the known molecular diversity of CD44 and provide another experimental model in which isoform specific functions can be investigated.

Amino Acid Sequence↗
PubMed1991

Transcripts encoding mouse CD44 (Pgp-1, Ly-24) antigen: strain variation and induction by mitogen.

The cell surface molecule CD44, thought to be a cell surface receptor for hyaluronic acid, is expressed by thymocytes and peripheral T cells. Following T cell activation with mitogens or antigens, surface expression of CD44 increases. This increase in CD44 cell surface expression has been used as a means of identifying memory T cells in vivo. In this report, using Northern analysis, we have quantitated mouse CD44 transcripts in thymocytes and a cloned T hybridoma cell line. In contrast to a recent report by Nottenburg et al. (Proc. Natl. Acad. Sci. USA 1989. 86: 8521), we show that in all instances CD44 transcripts are polyadenylated. In all cells studied, three major mRNA species of approximately 4.5, 3.5 and 1.6 kb are detected. After stimulation with phorbol 12-myristate 13-acetate (PMA), there is a de novo protein synthesis-dependent increase in the level of CD44 transcripts. The increase in CD44 transcripts precedes the increase in cell surface expression. In contrast to CD44, PMA stimulation results in a decrease in the level of Thy-1 transcripts. Thymocytes from different mouse strains vary in their level of CD44 cell surface expression and Northern analysis indicates that this mouse strain variation correlates with a corresponding difference in the level of CD44 transcripts.

Animals↗
PubMed1991

Expression of CD44 is repressed in neuroblastoma cells.

We have used cDNA subtractive cloning to identify a group of human genes that are expressed in diverse differentiated derivatives of neural crest origin but not in neuroblastoma cell lines. One of these genes was identified as CD44, which encodes an integral membrane glycoprotein that serves as the principal receptor for hyaluronate and participates in specific cell-cell and cell-extracellular matrix interactions. The repression of CD44 expression in neuroblastoma cell lines might be relevant to their high metastatic potential. We have cloned full-length cDNAs corresponding to CD44 trancscripts and identified a novel splice variant of CD44 lacking 31 amino acids of the extracellular domain. As a first step toward analysis of CD44 downregulation in neuroblastoma cells, we have mapped the CD44 RNA initiation site and analyzed the structure of the upstream regulatory region. We constructed a series of plasmids containing different amounts of CD44 upstream regulatory region linked to the bacterial chloramphenicol acetyltransferase gene and then analyzed their ability to promote transcription in neuroblastoma and melanoma cells. We found that a DNA segment including about 150 bp of the CD44 upstream region and the 5' end of the gene itself was sufficient to induce substantial transcription of the chloramphenicol acetyltransferase gene in both neuroblastoma and melanoma cells. Several upstream cis-acting elements contribute to the downregulation of CD44 in neuroblastoma cells, the most prominent being a 120-bp DNA fragment located 450 bp upstream to the RNA initiation site. Our data suggest that multiple factors might be involved in downregulation of CD44 in neuroblastoma cells.

Amino Acid Sequence↗
PubMed1992

Mechanism of peripheral T cell activation by coengagement of CD44 and CD2.

A number of CD44 antibodies are known to augment peripheral T cell proliferation stimulated with suboptimal concentrations of activating pairs of CD2 mAb. These findings have implicated the CD44 adhesion receptor in the activation of peripheral T cells via CD2. We have investigated early events after CD44 and CD2 coengagement on peripheral T cells. CD44 and CD2 coengagement resulted in enhanced [Ca2+]i mobilization. However, the increase in [Ca2+]i mobilization did not occur until at least 3 min after CD2 and CD44 coengagement, suggesting that other events precede the elevation in [Ca2+]i. Using a T cell/fibroblast adhesion assay, we could demonstrate a dramatic increase in T cell adhesiveness after about 1 min after CD44 and CD2 coengagement. The increase in T cell adhesiveness was comparable to that induced by PMA. In the absence of antibodies or treatment with mAb directed to other T cell surface Ag, there was little if any adhesion between unstimulated peripheral T cells and fibroblasts. Enhancement of T cell adhesiveness through CD44 engagement was not mediated by a direct effect on lymphocyte-function associated Ag-3, the known ligand of CD2. However, cross-linking of CD44 resulted in epitopic modulation of CD2 as demonstrated by the increased expression of the T11(3) activation epitope. Furthermore, anti-CD44 could substitute for anti-T11(2) in the activation of peripheral T cells via CD2. These results suggest that CD44 ligation has profound effects on CD2-mediated events by inducing epitopic modulation of CD2.

Antigens, CD↗
PubMed1989

Dual role of the CD44 molecule in T cell adhesion and activation.

Studies of T cell adhesion and activation reveal two new functions of the CD44 molecule, a molecule now recognized to be identical to three molecules of functional interest: Pgp-1, Hermes, and extracellular matrix receptor type III (ECMRIII). By screening for mAb which inhibit T cell adhesion to E, we have identified a functionally unique CD44-specific mAb, NIH44-1, which partially inhibits T cell rosetting by binding to CD44 on the E. NIH44-1, which immunoprecipitates a protein of 85 to 110 kDa with broad tissue distribution, was determined to be specific for CD44 based on comparison of its tissue distribution with multiple CD44-specific reference mAb and sequential immunoprecipitation with such mAb. Anticipating a role for many adhesion molecules in signal transduction, we studied the effect of CD44 mAb on T cell activation and observed that CD44 mAb dramatically augments T cell proliferation induced by CD3- and CD2-receptor-mediated activation. The augmentation of the response to immobilized CD3 mAb by exhaustively monocyte-depleted T cells indicates that augmentation can be mediated by binding to the T cell. Thus, our studies demonstrate specific new roles for CD44 in T cell adhesion and activation. Furthermore, we suggest that: 1) CD44 has a role in adhesion of cells of multiple lineages; and 2) CD44 may participate in adhesion not (only) by functioning as an adhesion receptor but rather by serving as an anchorage site for other adhesion molecules.

Adjuvants, Immunologic↗