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Results for “CD3 Complex”

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PubMed1996

Cytotoxic activity against tumour cells mediated by intermediate TCR cells in the liver and spleen.

Morphological and phenotypic characterization in previous studies has indicated that intermediate (int) T-cell receptor (TCR) cells or T natural killer (TNK) cells may stand at an intermediate position between NK cells and high TCR cells of thymic origin in phylogenetic development. In this study, a functional study on cytotoxic activity against various tumour targets was performed in each purified subset. When a negative selection method entailing in vivo injection of anti-asialo GM, antibody or anti-interleukin (IL)-2R beta monoclonal antibody (mAb) was applied, IL-2R beta 1 CD3 NK cells were found to have the highest NK activity while IL-2R beta 1 int CD3 (or TCR) cells had a lower level of the NK activity. High CD3 cells (freshly isolated) did not have any such activity. Sorting experiments further revealed that the NK function mediated by int CD3 cells was augmented when they were exposed to anti-CD3 mAb. anti-TCR alpha beta, or anti-TCR-delta mAb. This phenomenon was not observed in NK cells and high CD3 cells. More importantly, when anti-CD3 mAb (or anti-TCR mAb) was added to the assay culture, int CD3 cells became cytotoxic against even NK-resistant tumour (Fc gamma R-. Fas+) targets. Liver mononuclear cells or int CD3 cells exposed to anti-CD3 mAb for 6 hr showed an elevated level of perforin in their cytoplasms. The present results suggest that int CD3 cells are usually non-cytotoxic against various tumours but become functional after being stimulated via the TCR CD3 complex.

Animals↗

PubMed1994

Retention of unassembled components of integral membrane proteins by calnexin.

Quality control mechanisms prevent the cell surface expression of incompletely assembled multisubunit receptors such as the T cell receptor (TCR). The molecular chaperone function of calnexin (IP90, p88), a 90-kilodalton protein that resides in the endoplasmic reticulum (ER), in the retention of representative chains of the TCR-CD3 complex in the ER was tested. Truncation mutants of calnexin, when transiently expressed in COS cells, were exported from the ER and either accumulated in the Golgi or progressed to the cell surface. CD3 epsilon chains cotransfected with the forms of calnexin that were not retained in the ER exited the ER and colocalized with calnexin. Since engineered calnexin determined the intracellular localization of the proteins associated with it, it is concluded that calnexin interacts with incompletely assembled TCR components and retains them in the ER.

Amino Acid Sequence↗

PubMed1996

CD3-CD28 costimulation as a means to avoiding T cell preactivation in bispecific monoclonal antibody-based treatment of ovarian carcinoma.

One of the major limitations to the immunotherapy of ovarian carcinoma based on the use of anti-CD3/antitumor bispecific monoclonal antibodies (bi-mAb) is the need for preactivation of effector cells ex vivo, because cross-linking of the T cell receptor-CD3 complex per se may lead to T-cell unresponsiveness or even apoptosis. The bi-mAb OC/TR, which recognizes the folate-binding protein (FBP) overexpressed in 90% of ovarian carcinomas and the CD3 molecule on T cells, has demonstrated efficacy in a clinical setting. Here we investigated the possibility of delivering accessory signals to OC/TR-retargeted peripheral blood mononuclear cells (PBMCs) via an anti-CD28 mAb or an anti-FBP/anti-CD28 bi-mAb. Coculture of resting PBMCs from healthy donors with OC/TR, anti-FBP/anti-CD28 bi-mAb, and FBP+ tumor cell lines resulted in a highly activated phenotype of effector cells and in a dramatic in vitro growth inhibition of the target cells without an increase in OC/TR-redirected lysis. Whereas both the CD4 and CD8 T cell subsets were involved in the growth inhibition, only the CD8 subpopulation accounted for the cytotoxic activity. The in vitro tumor growth inhibition was mediated mainly by soluble factors, which were active on both FBP+ and FBP- ("bystander effect") cell lines. Activation and antitumor activity were also observed, albeit to a lesser extent, using OC/TR and monospecific bivalent anti-CD28 mAb. In vitro analysis demonstrated that cross-linking between tumor and effector cells for at least 24 h was needed to achieve T-cell activation and development of antitumor activities. Thus, ex vivo CD3-CD28 costimulation on resting PBMCs might be of therapeutic utility for local treatment of minimal residual disease.

Antibodies, Bispecific↗

PubMed1995

Expression and function of a CD3-like molecule on normal and abnormal human parathyroid cells.

BACKGROUND: Normal and abnormal human parathyroid tissue express the T-lymphocyte protein CD4, and parathyroid and lymphocyte cells show similarities with respect to mechanisms of calcium permeability and regulation of the cytoplasmic calcium concentration. METHODS: Anti-Leu4, a monoclonal antibody recognizing the T-lymphocyte glycoprotein complex CD3, is used to immunohistochemically stain normal and abnormal human parathyroid cells and to explore influences on the parathyroid hormone (PTH) secretion of enzymatically dispersed parathyroid cells. RESULTS: Parathyroid glands of patients with different forms of hyperparathyroidism displayed variable expression of the anti-CD3 reactive complex. The stainings correlated both positively and inversely to immunoreactivity for a previously defined calcium sensor, the decreased expression of which may constitute a molecular basis for hyperparathyroidism. Incubation of parathyroid cells with the anti-Leu4 antibody inhibited PTH secretion and reduced its sensitivity to external calcium without influence on parathyroid cytoplasmic calcium concentration. CONCLUSIONS: The results suggest that the human parathyroid cells express a CD3-like molecule with the ability to interact in PTH release.

Adenoma↗

PubMed1994

Functional expression of human CD28 in murine T cell hybridomas.

CD28 is a 44 kDa Ig superfamily cell surface molecule expressed on most mature T cells. Through its interaction with the recently identified B7/BB1 counter-receptor, it is believed to play an important role as a co-stimulator of T cells along with the TCR-CD3 complex. Activation of T cells with CD28 mAbs synergizes with TCR-CD3 and CD2 stimulation, resulting in long term T cell proliferation, differentiation of cytotoxic T cells and production of large amounts of cytokines. In order to further delineate the role of CD28 in signal transduction and T cell activation, human CD28 was transfected into CD3+ murine T cell hybridomas. High levels of cell surface CD28 expression was achieved by protoplast fusion. The transfected molecule retained all the native CD28 mAb epitopes found on human T cells. In these transfectants, CD28 mAbs, similarly to CD3 mAbs, were able to induce Ca2+ mobilization, IL-2 promoter induction (measured as beta-galactosidase activity in T cells hybridomas pre-transfected with the IL-2-lac Z reporter gene), IL-2 secretion, TNF alpha production and apoptosis (observed as growth arrest and genome fragmentation). The parental host cells, or cells transfected with vector alone, responded only to mAbs to CD3. IL-2 secretion in the transfectants was obtained using either an IgM mAb to CD28 or IgG mAbs presented on the surface of IgG-FcR+ B lymphoma cells. Optimal activation via CD28 was inhibited by suboptimal concentrations of soluble CD3 mAb, suggesting an interaction between the two pathways. The immunosuppressive drugs Cyclosporin A and FK506 completely blocked CD28 and CD3 mediated IL-2 production in these transfectants whereas rapamycin had only a partial inhibitory effect. Finally, since the transfected human CD28 molecule confers full functional responsiveness to the murine T cell hybridomas without the need for costimulators such as PMA, this model is ideal for studying the structure-function relationships of the CD28 molecule as well as the transmembrane and cytoplasmic associations implied in CD28 signaling.

Animals↗

PubMed1990

Fibronectin promotes proliferation of naive and memory T cells by signaling through both the VLA-4 and VLA-5 integrin molecules.

The capacity of purified fibronectin to costimulate human T cell DNA synthesis was examined. Low concentrations of immobilized fibronectin, but not soluble fibronectin, augmented anti-CD3-induced proliferation of highly purified human T cells. In the absence of anti-CD3 stimulation, immobilized fibronectin did not induce T cell proliferation alone or in the presence of IL-2 or phorbol dibutyrate. Although fibronectin is present in high concentrations in the serum, immobilized fibronectin was able to costimulate T cell proliferation when cells were cultured in serum-containing medium. Immobilized collagen type I did not enhance anti-CD3 stimulated T cell responses, whereas gelatin (denatured collagen) and laminin were able to enhance anti-CD3 stimulated T cell responses modestly. The effects of gelatin, however, appeared to be indirect, because it could not enhance responses in medium devoid of fibronectin. Immobilized fibronectin enhanced anti-CD3 induced proliferation of both CD45RA dim and CD45RA bright subsets within both the CD4+ and CD8+ subpopulations of T cells, although cells with the CD45RA dim phenotype were costimulated by lower concentrations of immobilized fibronectin. Enhancement of anti-CD3 induced proliferation by immobilized fibronectin was completely inhibited by a mAb to CD29, the integrin beta 1-chain (4B4) and not by a variety of other mAb. In contrast to its effects on proliferation, 4B4 only partially blocked T cell binding to anti-CD3 and fibronectin-coated macrowells. These findings suggested that the interaction between fibronectin and its receptor transduced a signal to the T cell and did not merely stabilize the interaction between anti-CD3 and the CD3 complex. Further experiments confirmed this observation. Thus fibronectin could enhance anti-CD3 responses when it was immobilized to a separate surface. The augmentation of anti-CD3 stimulated proliferation induced by immobilized fibronectin was also inhibited partially by mAb to either VLA-4 or VLA-5 and completely by a combination of the two mAb. The mAb to VLA-4 not only blocked the capacity of immobilized fibronectin to enhance anti-CD3-induced T cell proliferation but also directly costimulated T cell responses. Thus, at least two fibronectin receptors are involved in fibronectin-mediated costimulation of T cell proliferation. These studies indicate that signals are transduced through the fibronectin receptors, VLA-4 and VLA-5, that augment T cell responses and therefore implicate the extracellular matrix protein fibronectin as an important influence regulating T cell responsiveness in vivo.

Antibodies, Monoclonal↗

PubMed1993

CD3-induced preferential hydrolysis of polyphosphoinositides and calcium regulation of inositol phosphate metabolism in a permeabilized murine T cell clone.

Murine T helper cloned cells permeabilized with the bacterial lysin, tetanolysin, were used to investigate the role of intracellular Ca2+ in regulating myo-[2-3H] inositol phospholipid (InsPL) hydrolysis triggered upon perturbation of the T cell receptor-CD3 complex. [Ca2+] was controlled by a calcium/magnesium/EGTA buffer. Antibody (mAb) aggregation of CD3 induced InsPL hydrolysis in the absence of added Ca2+. However, stimulated InsPL hydrolysis increased with the free [Ca2+], reaching a maximum at 100-300 nM [Ca2+]. Ca2+ increased the overall efficiency of hydrolysis without changes in EC50 of the anti-CD3 mAb. The response diminished at > 300 nM [Ca2+] due to a mixed type inhibition. Ca2+ alone had no effect on inositol phosphate levels. Polyphosphoinositides were preferentially cleaved, since no accumulation of Ins(1)P/Ins(3)P was detected, indicating that direct hydrolysis of phosphatidylinositol did not occur, irrespective of the Ca2+ concentration. [Ca2+] above 300 nM shifted the relative amounts of CD3-induced inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) in favor of the latter. Unlabeled permeabilized cells exposed to > or = 100 nM [Ca2+] showed enhanced conversion of [3H]Ins(1,4,5)P3 to [3H]Ins(1,3,4,5)P4. In conclusion, InsPL hydrolysis is optimally triggered by CD3 perturbation at intracellular Ca2+ levels approximating those observed in intact resting lymphocytes (100 nM). Ca2+ concentrations similar to those triggered by InsPL-derived metabolites may inhibit InsPL hydrolysis and promote Ins(1,3,4,5)P4 production, thus controlling the amounts of Ins(1,4,5)P3.

Algorithms↗

PubMed1993

Difference in signal transduction pathway for IL-2 and IL-4 production in T helper 1 and T helper 2 cell clones in response to anti-CD3.

To elucidate Th2 cell clone activation mechanism through TCR-CD3 complex, we examined the reactivity of Th2 cell clones to soluble anti-CD3 in the absence of accessory cells or costimulator. The soluble anti-CD3 stimulated IL-4 production of Th2 cell clones as efficiently as specific Ag. IL-4 production of Th2 cell clones was consistent with the elevation of intracellular free Ca2+ concentration ([Ca2+]i). The elevation was slow and sustained but occurred consistently after the anti-CD3 stimulation in all Th2 cell clones tested. The [Ca2+]i elevation appeared to depend on Ca2+ influx because it could not be observed in Ca(2+)-free medium. Several chemicals such as cholera toxin, neomycin, and herbimycin A, which have been shown to block phosphatidylinositol-4,5-bisphosphate (PIP2) breakdown pathway or protein tyrosine kinase activation, exerted no effect on the IL-4 production. In accordance with these findings, neither PIP2 breakdown nor protein tyrosine phosphorylation was observed in Th2 cell clones stimulated with anti-CD3. The inclusion of anti-CD4 in culture and the depletion of protein kinase C (PKC) did not affect IL-4 production of Th2 cell clones either. These findings support a hypothesis that Th2 cell clones use a signaling pathway for IL-4 production that is independent of protein tyrosine kinase, PIP2 breakdown or PKC, and that the [Ca2+]i elevation is the only pathway common to an IL-2 production of Th1 cell subset.

Animals↗

PubMed1988

Characterization of granzymes A and B isolated from granules of cloned human cytotoxic T lymphocytes.

A human CD8+ CTL clone with cytolytic potential was shown to express two serine proteases, a 50-kDa homodimer and a 27-kDa monomer, which were purified from cytoplasmic granules. N-terminal sequencing of the purified proteins revealed that the 50-kDa homodimer is the gene product of the human Hanukah factor cDNA clone and that it represents the human homologue to granzyme A. Similarly, the 27-kDa protein was shown to be the serine esterase encoded by the human lymphocyte protease cDNA clone and corresponds to granzyme B. There was no evidence for the presence of other granzymes, in particular for the human homologues to murine granzymes C, D, E, and F. The substrate best cleaved by granzyme A was Gly-Pro-Arg-amido-4-methyl-coumarin after the Arg residue and the pH optimum was 8 to 8.5. Upon triggering of the TCR-CD3 complex with an anti-CD3 mAb, granzyme A was released into the culture medium. Furthermore, a granule-associated hemolytic activity was detected after salt extraction and partial purification of granule proteins. This suggests that hemolytically active human perforin can be obtained from inactive granules.

Amino Acid Sequence↗

PubMed2000

Increased expression of non-functional killer inhibitory receptor CD94 in CD8+ cells of myeloma patients.

Different MHC class I-specific killer inhibitory receptors (KIRs) are expressed in vivo by a minor fraction of activated memory CD8+ cells. It has been postulated that KIRs may 'fine-tune' specific responses by altering their threshold of activation by the TCR-CD3 complex. We have previously shown that, in multiple myeloma (MM) patients, a large fraction of peripheral blood CD8+ cells display the phenotype of chronically activated memory T cells (CD38+, HLA-DR+, CD25-, CD45R0+, CD28-). We investigated the expression of KIRs on MM T cells and determined their possible influence on cytolytic responses elicited via the CD3-TCR complex. The expression of CD94, a molecule that is part of a heterodimeric KIR recognizing the non-classical MHC surface HLA-E molecule, was almost threefold higher in MM T cells than in age-matched normal control subjects (P < 0.0001). CD94 expression was preferentially confined to CD8+ cells but not restricted to activated (HLA-DR+) and/or memory (CD45R0+) T cells. Unlike normal T cells, in which CD94 is assembled with glycoproteins of the NKG2 family to form functional receptors with activating or inhibitory properties, most CD94+ MM T cells were devoid of both the NKG2-A and NKG2-C glycoproteins detected in the inhibitory or activating form respectively. CD94 blockade did not significantly affect either T-cell proliferation or cytotoxic T-lymphocyte generation induced by the myeloma-derived cell lines NCI and RPMI 8226. Similarly, the cytolytic activity induced by direct anti-CD3-mediated targeting of MM T cells to FCR+ P815 target cells was unaffected by the addition of anti-CD94 and/or anti-NKG2-A/C monoclonal antibodies (mAbs). These data indicate that the large majority of MM CD8+ cells do not express a functional CD94 receptor. Thus, their ability to 'fine-tune' an appropriate immune response against tumour cells can be impaired.

Antibodies, Monoclonal↗

PubMed1994

Serine phosphorylation of a 67-kDa protein in human T lymphocytes represents an accessory receptor-mediated signaling event.

Phosphorylation on serine residues of a 67-kDa cytoplasmic protein (p67) occurs as an early signaling event after stimulation of resting human T cells via CD2 but not via TCR/CD3. Phosphorylation of p67 is, however, not restricted to CD2 stimulation because it can also be induced by costimulation through CD4 and CD8 coreceptors when approximated to the TCR-CD3 complex, suggesting a common signaling mechanism for these accessory receptors of the Ig superfamily. Because late functional responses of T cell activation like IL-2 production and DNA synthesis correlate with phosphorylation of p67, this intracellular event may represent an accessory receptor-mediated costimulatory second signal for human T cell activation. The biochemical characteristics (m.w. and isoelectric point) of p67 are identical with those of the actin binding protein L-plastin (Fimbrin), a cytoplasmic protein that contains two Ca2+ binding sites and a calmodulin binding domain. Moreover, p67 reacts specifically with an L-Plastin (Fimbrin) antiserum.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1990

The T cell receptor-associated protein is proteolytically cleaved in a pre-Golgi compartment.

The TCR consists of at least seven transmembrane chains: the clonotypic disulfide-linked alpha- and beta-chains, the invariant gamma-, delta-, and epsilon-chains, termed the CD3 complex, and the zeta-zeta homodimer. We have recently described an additional 26-kDa protein, which is transiently associated with newly synthesized mouse CD3 chains in the endoplasmic reticulum. The exact function of this protein, which we called TRAP (for TCR-associated protein) is not yet known; studies suggest however, that it may play a role in the assembly of the TCR complex. Here we report the properties of another protein which has a Mr of 16,000 and, like TRAP, can be coimmunoprecipitated from metabolically labelled murine T cells with antibodies against the chains of the CD3 complex. Kinetic analysis suggests a precursor-product relationship between TRAP and the 16-kDa protein: the latter starts appearing once TRAP begin to disappear. Having reached a maximal level at approximately 1 h after biosynthesis, it is rapidly lost. Agents that slow or block the disappearance of TRAP, delay or prevent the appearance and eventual disappearance of the 16-kDa protein. Incubation of immunoprecipitates containing gamma, epsilon, and TRAP in vitro at 37 degrees C results in the appearance of the 16-kDa protein. Employing HPLC peptide mapping we demonstrate that this 16-kDa protein is structurally related to TRAP. These results suggest that the removal of TRAP from the newly synthesized CD3 chains is accompanied by its proteolytic cleavage in a pre-Golgi compartment.

Animals↗

PubMed1991

Interactions between CD3 and Thy1 T cell activation pathways: blockade of CD3-mediated T lymphocyte activation induced by immobilized anti-Thy1 antibodies.

Resting murine T cell activation induced by either CD3 complexes or Thy1 molecules was investigated in vitro, using surface-bound anti-CD3 mAb as the stimulus. One mitogenic anti-Thy 1 mAb (G7) lost mitogenicity when presented to T cells immobilized on a plastic surface, even in the presence of phorbol ester. Moreover, T cell activation induced by immobilized anti-CD3 was potently blocked by coimmobilized anti-Thy 1 mAb. Nonmitogenic anti-Thy 1 mAb also blocked CD3-induced activation when coimmobilized with anti-CD3. Control experiments showed that anti-Thy 1 specifically blocked T cell activation, even in the presence of measurable and functional concentrations of plastic-bound anti-CD3. Coimmobilized anti-Thy 1 potently blocked IL2 secretion stimulated by anti-CD3. Addition of exogenous rIL2 completely prevented anti-Thy 1-mediated blockade. On the other hand, while completely blocking T cell proliferation, immobilized anti-Thy 1 only partially blocked secretion of IL3-like activity by the T cells. One IgM anti-Thy 1 mAb (2A3) induced secretion of IL3-like activity by T cells when immobilized in the absence of bound anti-CD3. These results indicate that extensive aggregation of Thy 1 molecules delivers a potent negative signal which antagonizes CD3-mediated T cell activation and growth.

Animals↗

PubMed1990

Induction of specific nonresponsiveness in unprimed human T cells by anti-CD3 antibody and alloantigen.

Fresh peripheral blood mononuclear cells exposed to alloantigen for 3-8 d in the presence of anti-CD3 antibodies showed no response after restimulation with cells from the original donor but remained capable of responding to third-party donors. Antigen-specific nonresponsiveness was induced by both nonmitogenic and mitogenic anti-CD3 antibodies but not by antibodies against CD2, CD4, CD5, CD8, CD18, or CD28. Nonresponsiveness induced by anti-CD3 antibody in mixed leukocyte culture was sustained for at least 34 d from initiation of the culture and 26 d after removal of the antibody. Anti-CD3 antibody also induced antigen-specific nonresponsiveness in cytotoxic T cell generation assays. Anti-CD3 antibody did not induce nonresponsiveness in previously primed cells. Nonresponsiveness induced by anti-CD3 did not appear to be associated with suppressor cell activation. Thus, co-stimulation of the T cell receptor-CD3 complex on unprimed T cells with a fluid phase anti-CD3 antibody and allogenic major histocompatibility complex antigens can induce either clonal anergy or clonal deletion. These results suggest novel approaches for achieving transplantation tolerance.

Antibodies, Monoclonal↗

PubMed1990

Freshly isolated Thy-1+ dendritic epidermal cells express T cell receptor gamma delta-CD3.

Within murine epidermis exists a population of Thy-1+ DEC which express membrane Thy-1 antigen, but lack CD8 or CD4 antigen. We examined freshly obtained non-cultured Thy-1+ DEC both by immunofluorescence and by biochemical techniques to identify the protein products of the T cell receptor (TCR) and the associated CD3 complex on these cells. Virtually all of the Thy-1+ DEC are brightly positive in CD3 expression with immunofluorescence using the monoclonal antibody 145-2C11. By immunoprecipitation, using this same antibody and polyclonal anti-TCR-gamma antibody, the only TCR heterodimer detected on the freshly isolated Thy-1+ DEC is the gamma delta heterodimer. These findings suggest that in the phenotype and TCR expression, Thy-1+ DEC are analogous to CD8-, CD4- early fetal thymocytes.

Amino Acid Sequence↗

PubMed1993

Multiple signal transduction pathways induce phosphorylation of serines 16, 25, and 38 of oncoprotein 18 in T lymphocytes.

A multitude of external signals induce extensive phosphorylation of Oncoprotein 18 (Op18), which suggests a putative role for this protein in signal transduction. We have recently identified two distinct proline-directed kinase families that phosphorylates Op18 with overlapping but distinct site preference. These two kinase families, mitogen-activated protein (MAP) kinases and cyclin-dependent cdc2 kinases, are involved in receptor- and cell cycle-regulated phosphorylation events, respectively. In the present study, site-specific phosphorylation of Op18 in response to stimulation of the antigen receptor-associated CD3 complex was analyzed in the Jurkat T cell-line. The results show that CD3-induced phosphorylation of Ser-25 of Op18, which is the primary MAP kinase phosphorylation site, can be induced by an apparently protein kinase C (PKC)-independent signal transduction pathway. We also demonstrate that Ser-16 of Op18 is specifically phosphorylated in response to the Ca2+ signal generated by CD3 stimulation or by the Ca2+ ionophore ionomycin. Ser-16 phosphorylation occurs independently of both PKC and MAP kinase activation. Using site-specific Op18 mutants and tryptic phosphopeptide mapping, we show that phosphorylation of Ser-16 of Op18 together with Ser-25, or Ser-25 and Ser-38, generates two Op18 phosphoisomers showing a dramatic electrophoretic retardation. In conclusion, site-mapping studies of Op18 reveal that CD3 stimulation results in an apparently PKC-independent activation of both the MAP kinase and a Ca(2+)-regulated kinase pathway, which results in phosphorylation of distinct sites of Op18. The data also pinpoints the specific phosphorylation events that result in electrophoretic retardation of Op18.

Amino Acid Sequence↗

PubMed1991

Structural similarity between Fc receptors and T cell receptors. Expression of the gamma-subunit of Fc epsilon RI in human T cells, natural killer cells and thymocytes.

The TCR complex is composed of a clonotypic heterodimer (Ti alpha:beta or gamma:delta) noncovalently associated with the CD3 complex (gamma, delta, and epsilon), and with one or more disulfide-linked dimers whose components are designated zeta and eta. zeta and eta are alternative transcripts of a common gene and are structurally related to the gamma-subunit of the FcR for IgE expressed on mast cells and basophils (Fc epsilon RI). Recent evidence suggests that gamma can also be expressed in natural killer cells and in a murine cytotoxic T cell line, CTLL. Because zeta, eta, and gamma have the potential to join together to form disulfide linked homo- and heterodimers, it has been postulated that alternative dimeric forms composed of these zeta-related subunits might subserve unique signal transducing functions in hematopoietic cells. We have used mAb reactive with zeta and gamma to systematically examine the expression of these zeta-related dimers in human T cells, NK cells, and thymocytes. Our results show that each cell type expresses characteristic combinations of zeta-related homo- and hetero-dimers, and are therefore consistent with the possibility that these subunits contribute to the functional heterogeneity of lymphocyte subsets.

Antibodies, Monoclonal↗

PubMed1991

Evidence that the CD45 phosphatase regulates the activity of the phospholipase C in mouse T lymphocytes.

The importance of the tyrosine phosphatase CD45 in the regulation of lymphocyte activation was first demonstrated using antibodies against the extracellular domain of CD45 in functional assays. More recently it was reported that CD45-negative mutants were nonresponsive to stimulation through the T cell receptor-CD3 complex. We have studied the effect of CD45 cross-linking on the early signals induced by CD3 in mouse T cells. We show that CD45 cross-linking inhibits the increase in inositol phosphates and cytoplasmic Ca2+ induced by cross-linking of CD3. This indicates that CD45 is involved in the regulation of phospholipase C.

Animals↗