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At least 19 recordsLinked to original sources
PubMed1993

Effects of low-doses of X-rays on the expression of human cell surface CD2 antigen in CD2+ CHO cells.

Thioguanine resistant CHO cells (HPRT-) were stably cotransfected with pSV2-gpt and pi H3-CD2 vectors using the calcium phosphate coprecipitation technique. The effects of single low doses of ionizing radiation were studied in a CD2+ CHO clone. The CD2+ phenotype responsible for binding sheep erythrocytes and rosette formation, was not affected by X-rays doses in the range 2-6 cGy. However, after 10 cGy of X-irradiation, 50% of the cells lost the CD2+ phenotype. These results suggest that this CD2+ clone might be a very sensitive indicator of very low X-ray doses. The implications of the phenotypic changes, observed after very low doses of irradiation, are discussed.

Animals↗
PubMed1987

The murine homologue of the T lymphocyte CD2 antigen: molecular cloning, chromosome assignment and cell surface expression.

The human T lymphocyte antigen CD2 (T11, sheep erythrocyte receptor) is expressed on all peripheral T cells and all but the most immature thymocytes. Experiments with monoclonal antibodies against CD2 suggest that CD2 is the cell surface receptor for a natural ligand involved in T cell proliferation. Clarification of the functional role of CD2 would be facilitated by the identification of CD2 in the mouse. However, antibodies that recognize the murine homologue have not been described. An alternative approach to the identification of the murine homologue was to use cross-species DNA hybridization, employing human CD2 cDNA as a probe. Clones encoding the murine homologue were isolated from a murine T helper cell cDNA library. The murine cDNA sequence encoded a predicted mature polypeptide of 322 amino acids that showed 54% identity with the predicted human sequence. As with the human polypeptide, the cytoplasmic domain was large, and rich in proline and basic residues. CD2 mRNA was expressed in murine thymus and spleen, and in the T cell line EL4. The murine CD2 gene was assigned to chromosome 3 by Southern blot analysis of mouse-hamster somatic cell hybrids. A rabbit antiserum raised against purified human CD2, precipitated from surface-labeled mouse thymocytes a glycoprotein of Mr 55,000-66,000 which decreased to Mr 35,000 on digestion with endo-beta-acetylglucosaminidase F. These sizes are consistent with those predicted for the murine CD2 antigen from the cDNA sequence.

Amino Acid Sequence↗
PubMed1989

Studies on the monocyte dependence of T-cell proliferation induced by monoclonal antibodies directed against regions I and II of the CD2 antigen.

We produced three murine monoclonal antibodies (mAb) directed against the human T-cell differentiation antigen CD2 (formerly T11) and analysed their epitope specificity by E-rosette inhibition, cross-blocking and proliferation-induction experiments. When added together, two mAb (both IgG1 kappa) were able to induce proliferation in peripheral blood T cells. This proliferation was found to be strictly dependent on the presence of monocytes. The polymorphism of Fc receptors (FcR) expressed on human monocytes for murine IgG1 antibodies, which is readily demonstrable in anti-CD3-induced T-cell activation, was not found in the anti-CD2-driven system. Moreover, mAb directed against the 40,000 MW FcRII were unable to inhibit proliferation induced by the mitogenic anti-CD2 combination. Still, F(ab')2 fragments of the mitogenic anti-CD2 antibody combination could not initiate T-cell mitogenesis, despite their ability to induce a rise in the free intracellular [Ca2+]. The contributions of monocytes and of antibody Fc moieties to T-cell proliferation, induced by combinations of anti-CD2 mAb, will be discussed.

Antibodies, Monoclonal↗
PubMed1992

Regulation of D-3 phosphoinositides during T cell activation via the T cell antigen receptor/CD3 complex and CD2 antigens.

An immediate consequence of T cell activation via the T cell receptor (TcR)/CD3 complex and CD2 antigen is the hydrolysis of phosphatidylinositol-(4,5)-bisphosphate and the generation of inositol-(1,4,5)-trisphosphate and diacylglycerol which then regulate intracellular calcium and protein kinase C. Changes in cellular levels of phosphoinositides phosphorylated on the D-4 and D-5 position during T cell activation have been well documented. Recently it has been proposed that phosphoinositides phosphorylated on the D-3 position of the inositol ring by a novel phosphoinositide (PI) 3 kinase may also be important in cell activation. In the present study we have examined the levels and regulation of D-3 phosphoinositides in T cells activated by the TcR/CD3 complex and CD2 antigens. The data show the existence of phosphatidylinositol-(3)-monophosphate [PtdIns(3)P], phosphatidylinositol-(3,4)-bisphosphate [PtdIns(3,4)P2] and phosphatidylinositol-(3,4,5)-trisphosphate [PtdIns(3,4,5)P3] in T cells. Activation of the TcR/CD3 complex or CD2 antigen results in modulation of PtdIns(3,4)P2 and a putative PtdIns(3,4,5)P3 in T cells but does not change levels of PtdIns(3)P. These data provide the first evidence that lipid products of a PI3 kinase exist in T cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

Structure of domain 1 of rat T lymphocyte CD2 antigen.

The CD2 antigen is largely restricted to cells of the T-lymphocyte lineage and has been established as an important adhesion molecule in interactions between human T lymphocytes and accessory cells. In the adhesion reaction, CD2 on T cells binds to LFA-3 on other cells, with binding through domain 1 of CD2. CD2 can also be a target for the delivery of mitogenic signals to T lymphocytes cultured with combinations of anti-CD2 antibodies. Two predictions that are contradictory have been made for the structure of CD2 domain 1. One suggests an immunoglobulin (Ig) fold, on the basis of sequence patterns conserved in the Ig-superfamily (IgSF), whilst the other proposes a pattern of alternating alpha-helices and beta-strands, on the basis of secondary structure predictions. Thus CD2 domain 1 is an important test case for the validity of IgSF assignments based on sequence patterns. We report here the expression of domain 1 of rat CD2 in an Escherichia coli expression system and have determined a low-resolution solution structure by NMR spectroscopy.

Amino Acid Sequence↗
PubMed1989

Transmembrane signalling via the T cell antigen receptor heterodimer and the CD2 antigen. A synergistic pathway for activation of T cells.

T cell surface proteins involved in transmembrane signalling resulting in the activation of T cells were investigated utilizing as probes monoclonal antibodies directed at T cell surface antigens. Here we report that mAbs that react with a framework determinant of alpha/beta heterodimer of T cell receptor for antigen, anti-TCR-1, and those with the SRBC-binding epitope of the CD2 antigen, OKT11, are synergistic in promoting T cell proliferation. The proliferative response is dependent upon crosslinking of anti-TCR-1 and OKT11, and is associated with a significant increase in the concentration of intracellular free calcium in T cells. Moreover, EGTA and a direct (staurosporine) or a competitive (1-[5-isoquinolinylsulfonyl]-2-methyl piperazine) inhibitor of protein kinase C prevents T cell proliferation accomplished with crosslinked anti-TCR-1 and OKT11. Our findings, in addition to demonstrating the synergism between the signals initiated via the T cell receptor for antigen and the CD2 antigen, suggest a role for calcium and protein kinase C in the transduction of signals generated with crosslinked anti-TCR-1 and OKT11.

Alkaloids↗
PubMed1989

Activation of T lymphocytes via monoclonal antibodies against rat cell surface antigens with particular reference to CD2 antigen.

In the rat, monoclonal antibodies (mAbs) against the T-lymphocyte receptor (TCR), CD3 antigen and CD2 antigen are mitogenic for T lymphocytes. Antibodies against CD43 (leukosialin) and CD5 are not, but can enhance the effects of other stimuli. Activation of a T-lymphocyte cell line in terms of triggering an increase in free cytoplasmic Ca2+ [( Ca2+]i) was mediated by mAbs against Class 1 MHC and CD4 in addition to the mitogenic mAbs. In the presence of non-activating levels of anti-TCR mAb a strong synergistic signal was seen with anti-CD4, but incubation with anti-CD4 prior to activation with anti-CD3 inhibited the CD3 signal. Stimulation of DNA synthesis in resting T cells via anti-CD2 mAbs required a combination of two non-competitive antibodies and addition of a third anti-CD2 mAb inhibited the activation. The anti-CD2 mAbs were active on all types of mature T cells from peripheral lymphoid organs and the thymus, but cells in the thymus that lacked a TCR could not be activated via CD2. Rat CD2 was transfected into Jurkat cells and cross-linking with anti-rat CD2 mAbs gave an increase in [Ca2+]i similar to that seen with an anti-human CD3 mAb. All three types of anti-rat CD2 mAbs gave a signal including the mAb that inhibited mitogenesis. Signal transduction via CD2 was not seen in L cells and was only weakly observed in TCR-ve Jurkat cells that had been transfected with rat CD2. The cytoplasmic domain of transfected CD2 was shown to be important for the signal transduction since no increase in [Ca2+]i could be triggered in cells expressing mutant CD2 that lacked the cytoplasmic domain. Mutant forms with increasing lengths of cytoplasmic domain showed functions that progressively approached that of the native function.

Amino Acid Sequence↗
PubMed1988

Stable expression of the cDNA encoding the human T lymphocyte-specific CD2 antigen in murine L cells.

The human CD2 antigen is a T lymphocyte cell surface glycoprotein that has been implicated in both T lymphocyte adhesion and activation. The requirement for a T lymphocyte-specific factor(s) in the mechanism of signal transduction initiated via the CD2 antigen has been explored using murine L cells transfectants that stably express the human CD2 antigen at the cell surface. Such transfectants express the three CD2 epitopes previously defined on human T lymphocytes. However, combinations of CD2 monoclonal antibodies, that stimulated an increase in the cytoplasmic calcium concentration of the human T cell line Jurkat, failed to induce a similar signal in the transfectants. These results indicate that the transfected CD2 antigen cannot alone transduce intracellular signals in response to stimulatory combinations of CD2 monoclonal antibodies, and suggest that the functional CD2 antigen expressed on human T lymphocytes requires the association of another, as yet undefined factor(s).

Animals↗
PubMed1991

Enhanced expression of CD2 antigen on lung T cells.

CD2 molecules not only function in the adhesion of T cells to other cell types but also in the activation of T cells via an alternative pathway. To investigate the possible roles of CD2 molecules in the activation and accumulation of lung T cells, using monoclonal antibodies and a flow cytometer we evaluated CD2 antigen expression on lung and blood lymphocytes in 10 normal subjects, 30 patients with pulmonary sarcoidosis, 7 patients with interstitial pneumonia associated with collagen vascular disease, 5 patients with farmer's lung disease, and 8 patients with Crohn's disease. The mean fluorescence intensity (MFI) of CD2 on lung T cells obtained by bronchoalveolar lavage (BAL) was significantly higher than that on blood T cells in all study groups except the control group. In patients with pulmonary sarcoidosis this enhancement of the expression of CD2 antigen was observed only on CD4+ T cells. Since ligands for CD2 are present on immunocompetent cells of other types in the local pulmonary milieu, these results suggest that increased expression of CD2 molecules could facilitate the communication and interaction of lung T cells with their environment in the lung and thereby possibly contribute to the local accumulation of T cells.

Adult↗
PubMed1995

A role for phosphatidylinositol 3-kinase in the regulation of beta 1 integrin activity by the CD2 antigen.

The rapid and reversible upregulation of the functional activity of integrin receptors on T lymphocytes is a vital step in the adhesive interactions that occur during successful T cell recognition of foreign antigen and transendothelial migration. Although the ligation of several different cell surface receptors, including the antigen-specific CD3/T cell receptor complex, the CD2, CD7, and CD28 antigens, as well as several chemokine receptors, has been shown to rapidly upregulate integrin function, the intracellular signaling events that initiate this increase in adhesion remain poorly defined. In this study, we have used DNA-mediated gene transfer to explore the role of phosphatidylinositol 3-kinase (PI 3-K) in the upregulation of beta 1 integrin functional activity mediated by the CD2 antigen. CD2 was expressed in the myelomonocytic cell line HL60, which expresses beta 1 integrins that mediate adhesion to fibronectin and VCAM-1 in an activation-dependent manner. Antibody stimulation of CD2 expressed on HL60 transfectants resulted within minutes in increased beta 1-mediated adhesion to fibronectin and VCAM-1 at levels comparable to that obtained upon stimulation with the phorbol ester PMA. A role for PI 3-K in CD2-mediated increases in beta 1 integrin function is suggested by: (a) the ability of the PI 3-K inhibitor wortmannin to completely inhibit CD2-induced increases in beta 1 integrin activity; (b) the association of PI 3-K with CD2; and (c) induced PI 3-K activity upon CD2 stimulation. The mode of association of PI 3-K with CD2 is not mediated by tyrosine phosphorylation-dependent binding of PI 3-K via SH2 domains, since: (a) PI 3-K is associated with CD2 in unstimulated cells; (b) CD2 stimulation fails to increase the amount of associated PI 3-K; and (c) the CD2 cytoplasmic domain lacks tyrosine residues. A role for both protein kinase C and cytoskeletal rearrangements in CD2 regulation of integrin activity is also suggested, since a PKC inhibitor partially inhibits CD2-induced increases in beta 1 integrin function, and CD2 stimulation increases F-actin content in a wortmannin-sensitive manner. Analysis of human peripheral T cells indicated that CD2 stimulation also results in PI 3-K-dependent upregulation of beta 1 integrin activity. Thus, these results demonstrate that CD2 can function as an adhesion regulator in the absence of expression of the CD3/T cell receptor complex; and directly implicate PI 3-K as a critical intracellular mediator involved in the regulation of beta 1 integrin functional activity by the CD2 antigen.

Actins↗
PubMed1988

Oxidative mitogenesis: participation of CD2 antigen in the generation and/or transduction of obligatory accessory signals.

We investigated the role of cluster designation 2 (CD2) antigen in the activation of human T cells using either soluble phase or crosslinked monoclonal anti-CD2 antibodies, and oxidizing mitogens as probes. Soluble phase anti-CD2 inhibited oxidative mitogenesis when accessory signals were delivered with accessory cells and not when 12-O-tetradecanoylphorbol-13-acetate or interleukin 2 provided the required accessory signals. Soluble phase anti-CD2 also inhibited accessory cell-dependent increases in intracellular free calcium concentration and cell-to-cell contact among oxidizing mitogen-treated T cells and accessory cells. Crosslinked anti-CD2, on the other hand, generated the required accessory signals and functioned as an accessory cell substitute. Also, signals initiated by crosslinked anti-CD2 were able to replace accessory cell signals only, and not the mitogenic signals initiated with the oxidizing mitogens. Collectively, these findings indicate that the CD2 antigen participates in the generation and/or transduction of accessory signals obligatory for oxidative mitogenesis.

Antibodies, Monoclonal↗
PubMed1996

CD2 antigen expression on leukemic cells as a predictor of event-free survival after chemotherapy for T-lineage acute lymphoblastic leukemia: a Children's Cancer Group study.

We examined the prognostic impact of CD2 antigen expression for 651 patients with T-lineage acute lymphoblastic leukemia (ALL), who were enrolled in front-line Childrens Cancer Group treatment studies between 1983 and 1994. There was a statistically significant correlation between the CD2 antigen positive leukemic cell content of bone marrow and probability of remaining in bone marrow remission, as well as overall event-free survival (EFS) (P = .0003 and P = .002, log-rank tests for linear trend). When compared with patients with the highest CD2 expression level (> 75% positivity), the life table relative event rate (RER) was 1.22 for patients with intermediate range CD2 expression level (30% to 75% positivity) and 1.81 for "CD2-negative" patients (< 30% positivity). At 6 years postdiagnosis, the EFS estimates for the three CD2 expression groups (low positivity to high positivity) were 52.8%, 65.5%, and 71.9%, respectively. CD2 expression remained a significant predictor of EFS after adjustment for the effects of other covariates by multivariate regression, with a RER of 1.47 for CD2-negative patients (P = .04). Analysis of T-lineage ALL patients shows a significant separation in EFS after adjustment for the National Cancer Institute (NCI) age and white blood cell (WBC) criteria for standard and high-risk ALL (P = .002, RER = 1.67). The determination of CD2 expression on leukemic cells helped identify patients with the better and poorer prognoses in both of these risk group subsets. For standard risk T-lineage ALL, CD2-negative patients had a worse outcome (P = .0007, RER = 2.92) with an estimated 5-year EFS of 55.9% as compared with 78.3% for the CD2-positive patients. Thus, CD2 negativity in standard risk T-lineage ALL identified a group of patients who had a worse outcome than high-risk T-lineage ALL patients who were CD2 positive. The percentage of CD2 antigen positive leukemic cells from T-lineage ALL patients is a powerful predictor of EFS after chemotherapy. This prognostic relationship is the first instance in which a biological marker in T-lineage ALL has been unequivocally linked to treatment outcome.

Adolescent↗
PubMed1992

Molecular associations between the T-lymphocyte antigen receptor complex and the surface antigens CD2, CD4, or CD8 and CD5.

The T-cell antigen receptor (TCR) complex is the key structure involved in signal transduction in T cells. To analyze associations between the TCR complex and other molecules, immunoprecipitations were carried out, followed by phosphorylation of molecules in vitro by tyrosine kinases associated with the precipitated molecules. This provided a sensitive assay for molecular complexes, and associations were demonstrated between the TCR complex and the surface antigens CD2, CD4, or CD8 and CD5 in normal rat T cells. The complexes were readily seen in immunoprecipitates from Brij 96 but not Nonidet P-40 detergent extracts. The multimolecular complexes are associated with the internal tyrosine kinases p56lck and p59fyn. The presence of p56lck associated with CD4 or CD8 was also examined in early thymocytes, natural killer cells, and macrophages. The kinase was present in all cases except that of normal macrophages.

Animals↗
PubMed1996

CD2 antigen targeting reduces intragraft expression of mRNA-encoding granzyme B and IL-10 and induces tolerance.

We explored the hypothesis that CD2 antigen-specific therapy would reduce intragraft gene expression and facilitate the emergence of transplantation tolerance. This postulate was tested in a murine pancreatic islet cell allograft model in which a novel mAb directed at the CD2 antigen, RM2-2 anti-CD2 mAb (RM2-2 mAb), was used to regulate CD2 antigen-dependent antiallograft response. Peritransplant administration (day -1, 0, and day + 1 with respect to transplantation) of RM2-2 mAb resulted in significantly longer survival of DBA/2 pancreatic islet cell allografts in the B6AFl recipient compared with untreated recipients. RM2-2 mAb therapy facilitated the induction of antigen-specific tolerance: whereas retransplantation with the original donor strain (DBA/2) islet cell allograft was successful, retransplantation with a third-party donor (SJL) islet cell allograft was not. In vivo administration of RM2-2 mAb therapy resulted in a decrease in the percentage of T cells that coexpressed the CD2 antigen (demonstrated by two-color flow cytometry) and in a decrease in intragraft expression of cytotoxic cell specific granzyme B mRNA and IL-10 mRNA (detected by RT-PCR). Our data, in addition to demonstrating for the first time the efficacy of RM2-2 anti-CD2 mAb, suggest that CD2 antigen is a suitable target for the induction of transplantation tolerance.

Animals↗
PubMed1987

Direct evidence for a receptor-ligand interaction between the T-cell surface antigen CD2 and lymphocyte-function-associated antigen 3.

The recognition of foreign antigen by T lymphocytes requires direct contact with cells expressing the antigen. It has recently become clear that T lymphocytes can form conjugates with other cells in the absence of foreign antigen expression. Studies using monoclonal antibodies (mAbs) to inhibit conjugate formation have suggested that a portion of the antigen-dependent adhesion is mediated by T lymphocytes interacting with cells expressing lymphocyte-function-associated antigen 3 (LFA-3), a widely distributed cell surface protein. We have investigated antigen-independent adhesion by incorporating affinity-purified LFA-3 into the lipid membrane of an artificial target cell (ATC; a nylon-matrix vesicle with a lipid membrane). These vesicles are similar in size and density to intact cells, so that conjugates between cells and ATCs may be seen by light microscopy. ATCs expressing a density of LFA-3 similar to that on intact cells were found to form conjugates with T cells, but only if the T cells expressed the sheep erythrocyte receptor, CD2 (T11; LFA-2). Previous studies using mAbs have implicated the CD2 molecule in both adhesion and T-cell activation. ATCs prepared without surface protein or with purified HLA class I protein failed to interact with the CD2-positive T cells, indicating that the adhesion found was mediated by the LFA-3 molecule. Furthermore, mAb against LFA-3 or CD2 was able to block the LFA-3-mediated vesicle-cell interaction, whereas mAb against LFA-1 or HLA failed to inhibit the interaction. These results provide direct evidence that LFA-3 functions as an adhesion molecule by serving as a ligand for the CD2 molecule on T cells.

Antibodies, Monoclonal↗
PubMed1987

Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure.

A cDNA encoding the CD2 antigen has been isolated by a highly efficient technique based on transient expression in COS cells and adherence of cells expressing surface antigen to antibody-coated dishes. COS cells expressing a CD2 cDNA isolated by this method readily formed rosettes with sheep as well as human and other mammalian erythrocytes. Pretreatment of transfected COS cells with anti-CD2 antibody, or pretreatment of human erythrocytes with anti-LFA-3 antibody, abolished rosette formation.

Amino Acid Sequence↗