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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antigenic properties of S-100 beta-positive human T-lymphocytes (S-100 beta+ T-cells) were investigated by a double immunostaining technique employing an indirect immunoperoxidase method for cytoplasmic S-100 beta subunit and an immunoalkaline phosphatase method for cell surface antigens detected by various monoclonal antibodies to human lymphocytes. S-100 beta+ T-cells recognized by their diffuse intracytoplasmic immunoperoxidase reaction, also expressed CD2, CD3, CD8 antigens demonstrated by surface blue alkaline phosphatase reactivity, but not CD4, CD1, CD25 (interleukin-2 receptor), or HLA-DR antigens. However, they displayed a blastic change to T-cell mitogens, such as Concanavalin A(Con-A) and PHA, followed by the expression of CD25 and HLA-DR antigens. Under normal conditions, S-100 beta+ T-cells comprised approximately 5-22.8% of CD8+ cells amongst human peripheral blood mononuclear cells.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:Immunocytochemical characterization of S-100 beta-positive human T-lymphocytes by a double immunostaining method. 244 20

A subclone that had lost its IgG1 heavy chain was derived from a hybridoma cell line G17-2 that produces an anti-CD4 monoclonal antibody. This subclone was found to secrete a kappa light chain dimer (LCD) that could bind to the CD4 antigen expressed on a subset of human T lymphocytes. The light chain dimer bound to the same or similar epitope as the parental antibody since it blocked the binding of the parenteral anti-CD4 MAb but not the binding of another anti-CD4 MAb G19-2 that recognizes a different epitope. A rabbit anti-idiotype prepared against G17-2 crossreacted with the LCD and could block the antigen binding of both G17-2 and the LCD. Scatchard analysis performed with 35S-methionine or 3H-leucine labelled LCD showed an association constant Ka of 2.2 x 10(7) M-1, whereas the G17-2 parental antibody showed an association constant Ka of 2.5 x 10(9) M-1. These data indicate that the antigen specificity of the G17-2 parental MAb is conferred to a large extent by its light chain. The LCD was expressed on the surface of the LCD-producing hybridoma cells. Southern blot analysis with C kappa and J kappa probes demonstrated a single kappa transcription units which does not have any unusual DNA rearrangements and is distinct from the NS-1 kappa genes. To our knowledge, this LCD is unique in its ability to bind to a large (55,000 mol. wt) glycoprotein antigen.
Mol Immunol 1987 Dec
PMID:An immunoglobulin light chain dimer with CD4 antigen specificity. 244 6

Accumulating data suggest that the CD4 T-cell surface antigen transduces an independent intracellular signal during antigen-mediated T-cell activation. CD4 is physically associated with the internal membrane tyrosine protein kinase p56lck and can mediate, after antibody-mediated cross-linking, the rapid enzymatic activation of Lck, implying that CD4 signalling may involve changes in tyrosine protein phosphorylation. In this report, we describe that cross-linking of CD4 results in a series of rapid changes in intracellular tyrosine protein phosphorylation. The most prominent CD4-induced tyrosine phosphorylation change involved p56lck, which became extensively phosphorylated on the carboxy-terminal tyrosine residue 505 and, to a lesser extent, lymphocytes can transduce an intracellular signal resulting in tyrosine protein phosphorylation and strongly suggest that this property of CD4 is mediated through p56lck.
Mol Cell Biol 1989 Oct
PMID:Alterations in tyrosine protein phosphorylation induced by antibody-mediated cross-linking of the CD4 receptor of T lymphocytes. 247 26

The soluble form of human CD4, an HIV receptor molecule first detected on the surface of T cells, binds glycoprotein gp120, a coat protein of human immunodeficiency virus, and has potential value for the treatment of AIDS. As a first step toward providing the necessary quantities of this protein at an affordable price we report here on the production of functional, soluble human CD4 in transgenic mice. In these animals, a regulatory region derived from a murine gene encoding the whey acidic protein directs synthesis of human CD4 protein to the mammary gland of lactating animals where it is secreted into milk.
Mol Biol Med 1989 Aug
PMID:Functional human CD4 protein produced in milk of transgenic mice. 248 19

Mice homozygous for the autosomal recessive lpr gene have a disorder that results in autoimmunity and massive accumulation of T lymphocytes lacking CD4 and CD8 surface markers. These abnormal T cells exhibit constitutive tyrosine phosphorylation of a component of the CD3-T-cell receptor complex. We compared membrane tyrosine phosphorylation in lpr/lpr CD4- CD8- T cells and control T cells, lpr membranes exhibited a 7.3-fold increase (n = 16) in tyrosine phosphorylation of a 60-kilodalton protein. The increase was correlated with the Lpr but not the CD4- CD8- phenotype in that p60 phosphorylation was not increased in membranes from normal CD4- CD8- thymocytes. To identify the p60 in lpr cells, we examined the activity of several T-cell tyrosine-specific protein kinases. p56lck phosphorylation was only slightly increased in lpr membranes (2.2-fold; n = 16). Phorbol ester treatment of intact T cells before membrane isolation caused p56lck to migrate as pp60lck; however, pp60lck could be clearly distinguished from the pp60 in lpr cells by two-dimensional gel electrophoresis. The pp60 from lpr cells exhibited several isoforms at pH approximately 6.3 to 6.5. Although on two-dimensional gels pp60c-src had a pI (6.4 to 6.8) within a similar region, p60c-src mRNA, protein, and kinase activities were not increased in lpr cells. In addition, staphylococcal V8 proteolytic cleavage of the lpr pp60 isolated on two-dimensional gels yielded two major fragments, a pattern distinct from that of pp60c-src. However, by using an antiserum against the C-terminal sequence of c-Src and other related kinases, including p59fyn, the pp60 could be immunoprecipitated in greater amounts from lpr than from control T cells. When pp59(fyn) was selectively immunoprecipitated from T-cell membranes with specific antisera, its molecular weight, proteolytic cleavage pattern, and behavior on two-dimensional gels were identical to those of the pp60 from lpr cells. We conclude that p59(fyn) phosphorylation is increased in membranes from lpr/lpr CD4(-) CD8(-) T cells and that the increase is correlated with constitutive tyrosine phosphorylation and perhaps with the expansion of this unusual T-cell population.
Mol Cell Biol 1989 Nov
PMID:Tyrosine phosphorylation of a c-Src-like protein is increased in membranes of CD4- CD8- T lymphocytes from lpr/lpr mice. 255 44

Radiation leukemia virus (RadLV)-induced thymomas and malignant thymocytes from AKR mice have been shown to bind specifically retrovirus produced by these cell lines. Each lymphoma has been shown to have greatest specificity for cognate virus suggestive of an immune-specific receptor. The question of receptor identity has been addressed here using the RadLV-induced murine T cell lymphoma, C6VL/1, and antibodies specific for known cell surface determinants present on these cells. This lymphoma has been shown to bind both homologous and heterologous RadLV isolates, but to have greatest specificity for homologous retrovirus since homologous free virions can best block the interaction between cells and virus adhered to the wells of a microtitre plate. A clonotypic anti-TCR antibody has been shown to completely inhibit C6VL/1 binding to the homologous virus, RadLV/C6VL, but not to the heterologous virus, RadLV/VL3. Anti-CD4, anti-Thy1.2 as well as anti-H-2Kb and not anti-H-2Db antibodies were found to partially inhibit the interaction with both RadLV/C6VL and RadLV/VL3, yet neither of these virus preparations appears to be contaminated with Class I molecules as measured by radioimmunoassay. The binding interaction between C6VL/1 and RadLV/C6VL appears specifically to involve the TCR since antibody against the clonotypic site on the TCR heterodimer uniquely inhibits this interaction, while the binding of C6VL/1 to RadLV/VL3 appears to involve the H-2Kb molecule. When free virus particles were absorbed to receptors on C6VL/1, both RadLV/VL3 and RadLV/C6VL inhibited the binding of antibody to the TCR and CD4 molecules, while the binding of several anti-H-2Kb antibodies was specifically inhibited by RadLV/VL3. There are at least two known T cell surface structures involved in the interaction of the T cell lymphoma, C6VL/1, with RadLV. These are the TCR complex (comprising the TCR heterodimer and CD4), and the Class I H-2Kb molecule. Since the TCR molecule has been shown to comodulate with H-2Kb molecules when cells were cultured in the presence of anti-H-2Kb antibodies, and the CD4 and H-2Kb molecules have been shown to comodulate with the TCR on only a subpopulation of C6VL/1 cells treated with anti-TCR antibody, this suggests that the H-2Kb molecule may also be part of the larger molecular complex including CD4/8 which can form around the TCR heterodimer.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Immunol 1989
PMID:Binding of radiation leukemia viruses to a thymic lymphoma involves some class I molecules on the T cell as well as the T cell receptor complex. 255 69

Mononuclear phagocytes, including alveolar macrophages (AM), can be infected by the human immunodeficiency virus (HIV). Acting as accessory cells (AC), AM could infect CD4 lymphocytes through cell-to-cell contact and by inducing T cell proliferation, which increases lymphocyte susceptibility to infection. Using normal allogeneic T cells as responders, AM from infected individuals demonstrated an enhanced ability to stimulate a Con A and pokeweed mitogen lymphocyte proliferation assay compared with normal AM. Exogenous IL 1 enhanced the stimulation of a mitogen response by normal AM, but not from HIV-positive individuals, suggesting increased levels of this cytokine may explain the observed enhancement. However, increased IL 1 secretion by AM from HIV-infected patients could not be demonstrated, either in a bioassay or antigenically using an ELISA for IL-1 beta. Syncytia formation was observed when AM from asymptomatic HIV-positive individuals were cultured with normal T cells, suggesting viral transmission was occurring. Finally, in individual patients the stimulation of a mitogen response was inversely correlated with the CD4/CD8 ratio and total CD4 count, suggesting that enhanced AC function and CD4 cell depletion may be related in vivo. These findings indicate that enhanced AM accessory cell function is seen in HIV-infected individuals and could be a potential mechanism for CD4 cell depletion in the lung.
Am J Respir Cell Mol Biol 1989 Nov
PMID:Enhanced accessory cell function by alveolar macrophages from patients infected with the human immunodeficiency virus: potential role for depletion of CD4+ cells in the lung. 257 9

The regulation and expression of protein kinase C (PKC) and phosphomyristin C (PMC) (a principal substrate of PKC which is the major myristylated protein in lymphocyte and glioma lines that express it) in murine B and T lymphocytes were investigated. Both PMC and PKC are differentially regulated during T-cell development. The level of PMC expression is highest in CD4-8-, intermediate in CD4+8+, and lowest in J11d-, CD4, or CD8 single-positive thymocytes. PKC is equally expressed by all three thymic populations. In striking contrast to thymocytes, resting peripheral lymph node T cells and T-cell clones express little if any PMC and reduced levels of PKC. Neither PKC nor PMC is significantly induced upon the activation of lymph node T cells: treatment with anti-CD3 antibodies or anti-CD3 and interleukin-2 fails to induce PKC, whereas PMC is not induced by anti-CD3 alone and is only slightly induced by anti-CD3 and interleukin-2. In contrast to the situation with T cells, PMC and PKC are constitutively expressed at moderate levels in mature B cells. PMC is greatly increased in B-cell blasts generated by cross-linking the antigen receptor with anti-immunoglobulin. These results demonstrate that PMC and PKC are differentially regulated during the development and activation of B and T cells, suggesting that cellular events that rely upon PKC and PMC may differ during ontogeny and activation of different lymphocyte subsets.
Mol Cell Biol 1989 Sep
PMID:A major myristylated substrate of protein kinase C and protein kinase C itself are differentially regulated during murine B- and T-lymphocyte development and activation. 278 36

Mouse monoclonal antibodies (MAbs) have been prepared against rat T cell blasts. One MAb called MRC OX-40 recognized an antigen that differed from any previously described in that its expression was detected only on T blasts that also expressed the CD4 antigen. The OX-40 MAb did not detect an activation determinant of CD2 or CD4 molecules but recognized a distinct chain of mol. wt 50,000. The OX-40 MAb augmented T cell proliferation at late stages on in vitro responses. Other MAbs without obvious counterparts in other species were MRC OX-48 and MRC OX-49,50 which recognized cell surface molecules of mol. wts of about 95,000 and 90,000, respectively. The OX-48 antigen was not expressed on resting lymphocytes but was found on a subset of T and B blasts and also on other leucocytes. The OX-49,50 antigen was found on most haemopoietic cells but was expressed at greatly increased levels after lymphocyte activation and this was also the case for MRC OX-47 antigen which is of unknown Mr. The MRC OX-39 MAb was found to bind the rat IL-2 receptor; expression of this antigen was detected on thymic dendritic cells as well as on T blasts. The phenotype of rat T blasts compared to resting cells was also examined and changes in expression of L-CA, Thy-1, OX-2 and CD8 antigens were seen in addition to the changes found with the above MAbs.
Mol Immunol 1987 Dec
PMID:Antigens of activated rat T lymphocytes including a molecule of 50,000 Mr detected only on CD4 positive T blasts. 282 30

The differentiation of T lymphocytes inside the thymus results in the acquisition of MHC-restricted specific functions mediated by clonally distributed alpha/beta heterodimeric T-cell receptors (TcR). Genes encoding the alpha and beta subunits of the clonotypic receptor (Ti) are rearranged during thymic ontogeny and expressed in association with the monomorphic CD3 complex. The regulation of the expression of functional TcR along T-cell development is thus crucial to establish the ontogenic events involved in the acquisition and selection of T-cell repertoires. Current views support that CD3-alpha/beta heterodimers are acquired late in ontogeny on developing thymocytes already expressing CD4 and/or CD8 surface molecules, whereas CD4- CD8- early precursors, representing the major population in the embryonic thymus, do not yet express the alpha/beta TcR. However, a novel CD3-associated gamma/delta heterodimer has been recently identified on the surface of this "double negative" subset both in thymocytes and in MHC-unrestricted peripheral T cells, suggesting that alpha/beta and gamma/delta heterodimeric receptors are independently expressed on the surface of distinct thymic subpopulations during T-cell development. In contrast to these results, we report here that a major proportion of CD3+1-4-8- adult human thymocytes, included within the early "double negative" subset, express alpha/beta heterodimeric receptors, as assessed by flow cytometric analysis using a frame-work monoclonal antibody (WT.31) against the alpha/beta TcR complex. These and previous data showing that CD3+1-4-8- "double negative" thymocytes constitute a functional intermediate ontogenic stage in the differentiation of CD3+1-4+8-/CD3+1-4-8+ mature T cells from CD3-1-4-8- early prothymocytes further support the relevance of the CD3+1-4-8- transitional subset as immediate intrathymic precursors of alpha/beta TcR-bearing mature T cells. Therefore, developmental regulation of alpha/beta TcR expression was analyzed at the DNA, RNA, and protein levels in those different thymic subpopulations, defined by both functional and phenotypic criteria. Our results demonstrate that multiple Ti beta gene rearrangements and beta RNA messages are already evident at the early prothymocyte stage. Moreover, expression of relative levels of both Ti alpha and Ti beta functional RNA transcripts, similar to those observed in mature thymic cells, were also present in CD3+1-4-8- thymocytes. According with these data, immunoprecipitation analysis using a specific anti-Ti alpha antisera revealed that both alpha and beta molecules are expressed on CD3+ "double negative" and mature thymocytes, but not in prothymocytes
J Mol Cell Immunol 1988
PMID:Alpha/beta heterodimeric T-cell receptor expression early in thymocyte differentiation. 285 9


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