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Query: UNIPROT:P06889 (Mol)
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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 expression of mouse mammary tumor virus (MMTV) glycoproteins on the surface of stably infected mouse lymphoma cell line W7MG1 is dramatically increased by glucocorticoid hormones. A variant cell line, W7M.TS1, was selected from W7MG1 for its lack of expression of MMTV glycoproteins on the cell surface in response to treatment with glucocorticoid. Hormonal stimulation of MMTV RNA levels and hormone-induced cytolysis occurred normally in the variant cells. Furthermore, the rates of production of the precursor and mature forms of MMTV glycoproteins in the presence of glucocorticoid were similar in variant and wild-type cells. However, the accumulation of MMTV glycoproteins on the cell surface after hormone treatment was delayed by about 8 h in the variant relative to wild-type cells. The steady-state level of a constitutively expressed cellular protein, T200, on the variant cell surface was comparable to that on wild-type cells. However, in pulse-chase experiments, the appearance of newly synthesized T200 on the cell surface was delayed in the variant compared with wild-type cells. Another glucocorticoid hormone response, removal of H-2 class I antigens from the cell surface, was also delayed in the variant relative to wild-type cells, suggesting that turnover or internalization of cell surface glycoproteins may also be affected in the variant. The defects in the variant cell line were observed at 37 degrees C, but not at 31 degrees C; the variant cells grew normally at both temperatures. This variant phenotype defines a new genetic entity that is important for transport of glycoproteins between internal microsomal compartments and the cell surface.
Mol Cell Biol 1988 Feb
PMID:Temperature-sensitive transport of glycoproteins to the surface of a variant mouse lymphoma cell line. 283 39

We have previously reported that BSF-1 and an alloantibody to the B-cell differentiation antigen Lyb2 induce class II gene expression in two Ia negative pre-B-cell lines. Two questions were asked in these studies. The first question is whether the different stimuli which we and others have shown to induce class II expression in B-cells act via the same signal transduction mechanisms. The second question is whether the traditionally accepted pathway of B-cell differentiation, as defined by immunoglobulin (Ig) gene rearrangement, is applicable to other events that occur during B-cell differentiation. In this report, we have therefore examined a large panel of pre-B-cell lines at different stages of Ig gene rearrangement in an attempt to 1) identify the stage in B-cell development where class II gene expression occurs and where it becomes inducible by BSF-1 or anti-Lyb2, and 2) compare the signal transduction mechanisms used by these ligands. The majority of pre-B-cell lines tested did not express BSF-1 receptors and were consequently noninducible for class II by BSF-1; such cell lines were, however, inducible for class II expression by anti-Lyb2 and, in addition, by antibodies to the B220 membrane glycoprotein. The induction of class II molecules by BSF-1 and by anti-Lyb2 and anti-B220 differed in several respects: 1) Induction by anti-Lyb2 and anti-B220 did not require the presence of BSF-1 receptors; 2) BSF-1 selectively induced class II antigen expression while anti-Lyb2 and anti-B220 induced the expression of other surface markers as well; and 3) PGE2 inhibited BSF-1 but not antibody-mediated class II induction. Finally, the presence of receptors for BSF-1 and the baseline expression of cell surface Ia was shown to be unlinked to Ig gene rearrangement and expression in this series of pre-B-cell lines. The independent regulation of Ia and Ig genes observed here may reflect a branching rather than a linear pathway for B-cell differentiation. The differentiation of pre-B-cells to mature Ig-secreting cells should probably not be defined solely by rearrangement of Ig genes, since this is likely to represent an oversimplified view of B-cell differentiation.
J Mol Cell Immunol 1988
PMID:Differential induction of class II gene expression in murine pre-B-cell lines by B-cell stimulatory factor-1 and by antibodies to B-cell surface antigens. 315 Oct 65

It has recently been reported that liposomes containing membrane components from cytolytic T-cell (TC) clones could transfer lytic activity to noncytolytic T- and B-cell lines, strongly suggesting that TC possess membrane-associated molecules which noncytolytic lymphocytes lack and which play a critical role in the lytic mechanism. It was thus of interest to compare the membrane-associated proteins from TC-lines to those of noncytolytic helper T-cell (TH) lines to determine whether any membrane-associated proteins unique to TC could be identified. Cells from three TC-lines and four TH-lines were internally labelled with [35S]methionine and then disrupted by hypotonic lysis. Low-density (plasma membrane enriched) and high-density (endoplasmic reticulum enriched) membrane fractions were isolated from each cloned cell line and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Two proteins were identified which were prominent in the membrane fractions from each of the three TC-lines but not in the membrane fractions from any of the four TH-lines. One of these, p215, migrated as a broad band with an apparent mol. wt of 215,000. The other, p24, migrated as a sharp band, or tightly spaced doublet, with an apparent mol. wt of 24,000. Immunoprecipitation studies using monoclonal antibodies to T200, LFA-1, Thy 1 and Lyt 2 suggested that p215 was a variant of T200 found on TC-lines but not on TH-lines. Treatment of solubilized membrane proteins from TH-lines with anti-T200 precipitated a 185-kD protein seen on each of the TH-lines but on none of the TC-lines. In contrast, p24 was not precipitated by any of these monoclonal antibodies. It therefore appears that p24 represents a previously unidentified protein which is strongly expressed by TC but not by TH and is thus deserving of further study as to its functional significance.
Mol Immunol 1985 Jul
PMID:Comparison of membrane-associated proteins of murine cytolytic and helper cloned T-cell lines: identification of a protein, p24, prominent in membrane fractions from cytolytic but not helper T-cells. 316 97

A group of closely related high mol. wt (Mr) membrane glycoproteins is expressed with varying Mr on different subpopulations of lymphocytes, but the different Mr forms share the Ly-5 and T200 antigenic determinants. The Ly-5 molecule expressed by thymocytes has an Mr of 175,000 (175ly5). The antigenically related molecule on B-cells has an Mr of 210,000 (210ly5). It is not known whether the variations in size are due to differences in the polypeptide chain, post-translational modifications such as glycosylation, or both. In this report we examine the glycosylation of 175ly5 and 210ly5 to determine whether differences in carbohydrate moieties may account for the different Mr of these two Ly-5 species. Pronase digestion and alkaline borohydride treatment of these molecules labeled in the terminal galactose residues revealed that 210ly5 molecules have a more complex oligosaccharide pattern than 175ly5 molecules. While Ly-5 oligosaccharides from a T-cell tumor line were very similar to those of normal thymocytes, the pattern of Ly-5 carbohydrates from a B-cell tumor were somewhat different than those from normal B-cells. This report also presents evidence for O-linked sugars on Ly-5 molecules.
Mol Immunol 1985 May
PMID:Analysis of structural differences between Ly-5 molecules of T- and B-cells. 387 17

L-cells, which normally do not express the mouse lymphocyte T200 antigen, were transfected with DNA from the mouse T-cell lymphoma, BW5147, and a T200+ L-cell line isolated. The detection and enrichment of T200+ L-cells from a pool of transfectants was accomplished using monoclonal anti-T200 antibody and fluorescence-activated cell sorting. A subclone has been selected that is stable for expression of T200. The T200 molecules expressed by BW5147 and the T200+ L-cell are similar in size, around 190 Kd, compared to the 220-Kd B-cell form of T200. The BW5147 T200 molecule is 3000 daltons larger than the molecule expressed by the transfected L-cell, a size difference due to glycosylation moieties, since treatment of the molecules with Endoglycosidase F or treatment of cells with tunicamycin yields T200 molecules of the same size from the 2 cell sources. In comparison, the B-cell form of T200 retains a size difference of 25,000 daltons from the T-cell form after these treatments. Monoclonal antibodies specific for the B-cell form of T200 do not recognize the T200+ L-cell, providing further evidence that the T-cell form of T200 is expressed by the transfected L-cell.
Mol Immunol 1985 Oct
PMID:Stable expression of the mouse lymphocyte T200 antigen in L-cells after transfection with lymphoma DNA. 407 38

The experiments reported here were designed to answer two questions: (1) At what stage in normal pre-B cell development do immunoglobulin gene rearrangements occur?; and (2) Do heavy chain and kappa light chain genes rearrange in concert, or in an ordered sequence? To answer these questions, we studied immunoglobulin gene rearrangements in pre-B cell populations purified on the fluorescence-activated cell sorter (FACS). Gene rearrangement was assessed by measuring the loss of germ-line joining (J) segment-containing restriction fragments in B cells and two populations of pre-B cells. Large pre-B cells, the earliest identifiable cells in the B lineage, have rearrangements at both JH loci but do not have rearrangements at the kappa chain loci. Thus heavy chain rearrangement occurs concurrently with or prior to the expression of the surface marker B220, which we use to identify and isolate pre-B cells. Small pre-B cells, which include the immediate precursors of B cells, likewise have rearrangements at both JH loci, but may also have J kappa rearrangements. Approximately 1/3 of the J kappa loci are rearranged in small pre-B cells compared to 2/3 in kappa chain-expressing B cells. This suggests that the small pre-B cell population is actively undergoing kappa chain gene rearrangement. The striking asynchrony in heavy and light chain gene rearrangement is reflected at the level of gene expression; both pre-B cell populations synthesize mu chains but not kappa light chains. Heavy chain rearrangement is therefore a very early event in B lineage development and may begin in a cell not yet fully committed to the B lineage, whereas kappa rearrangement occurs just prior to the expression of surface immunoglobulin (sIg) and may be a rate-limiting step in the transition from pre-B to B cells.
J Mol Cell Immunol 1983
PMID:Immunoglobulin gene rearrangement during pre-B cell differentiation. 633 90

Src family protein tyrosine kinases (PTKs) play an essential role in antigen receptor-initiated lymphocyte activation. Their activity is largely regulated by a negative regulatory tyrosine which is a substrate for the activating action of the CD45 phosphotyrosine phosphatase (PTPase) or, conversely, the suppressing action of the cytosolic p50csk PTK. Here we report that CD45 was phosphorylated by p50csk on two tyrosine residues, one of them identified as Tyr-1193. This residue was not phosphorylated by T-cell PTKs p56lck and p59fyn. Tyr-1193 was phosphorylated in intact T cells, and phosphorylation increased upon treatment with PTPase inhibitors, indicating that this tyrosine is a target for a constitutively active PTK. Cotransfection of CD45 and csk into COS-1 cells caused tyrosine phosphorylation of CD45 in the intact cells. Tyrosine-phosphorylated CD45 bound p56lck through the SH2 domain of the kinase. Finally, p50csk-mediated phosphorylation of CD45 caused a severalfold increase in its PTPase activity. Our results show that direct tyrosine phosphorylation of CD45 can affect its activity and association with Src family PTKs and that this phosphorylation could be mediated by p50csk. If this is also true in the intact cells, it adds a new dimension to the physiological function of p50csk in T lymphocytes.
Mol Cell Biol 1994 Feb
PMID:Tyrosine phosphorylation of CD45 phosphotyrosine phosphatase by p50csk kinase creates a binding site for p56lck tyrosine kinase and activates the phosphatase. 750 3

We describe a potential regulatory mechanism for the transmembrane protein-tyrosine phosphatase CD45. Phosphorylation on both tyrosine and serine residues in vitro results in an activation of CD45 specifically toward one artificial substrate but not another. The activation of these kinases appears to be order dependent, as it is enhanced when phosphorylation of tyrosine precedes that of serine but phosphorylation in the reverse order yields no activation. Any of four protein-tyrosine kinases tested, in combination with the protein-serine/threonine kinase, casein kinase II, was capable of mediating this activation in vitro. The time course of phosphorylation of CD45 in response to T-cell activation is consistent with the possibility that this regulatory mechanism is utilized in vivo.
Mol Cell Biol 1994 Aug
PMID:Protein-tyrosine phosphatase activity of CD45 is activated by sequential phosphorylation by two kinases. 751 65

T cells that lack the CD45 transmembrane tyrosine phosphatase have a variety of T-cell receptor (TCR) signaling defects that are corrected by reexpression of wild-type CD45 or its intracytoplasmic domains. In this study, a chimeric molecule containing the myristylation sequence of Src and the intracellular portion of CD45, previously shown to restore function in CD45- T cells, was mutagenized to determine if membrane-associated CD45 tyrosine phosphatase activity is required to restore TCR-mediated signaling in CD45- T cells. Abolition of enzymatic activity by substitution of a serine for a critical cysteine in the first catalytic domain resulted in failure of this molecule to restore TCR signaling. Another mutation, in which a single amino acid substitution destroyed the myristylation site, resulted in failure of the chimeric molecule to partition to the plasma membrane. Although expressed at high levels and enzymatically active, this form of intracellular CD45 also failed to restore normal signaling in CD45- T cells. These findings strongly suggest that CD45's function in TCR signaling requires its proximity to membrane-associated tyrosine phosphatase substrates.
Mol Cell Biol 1994 Dec
PMID:CD45 tyrosine phosphatase activity and membrane anchoring are required for T-cell antigen receptor signaling. 752 53


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