Characterization of a new T-lineage glycoprotein expressed in mature T- cell leukemias and lymphomas

We identified a new human, T-lineage restricted glycoprotein of molecular weight 120 Kd that is expressed primarily in mature T-cell malignancies. The antigen, named TCA-1 (T-cell cytoplasmic antigen), is an intracellular glycoprotein found mainly in the Golgi stacks, although a few cell lines also display surface membrane TCA-1. Many but not all T-cell neoplasms express this antigen. The antigen is absent from neoplastic and normal human tissue outside the T-lymphocyte lineage. TCA-1 was identified by murine monoclonal antibodies produced after immunization of mice with T-cell chronic lymphocytic leukemia cells. The glycoprotein is a monomer containing approximately 4% N- linked carbohydrate with terminal D-galactose residues. Partial amino acid sequence analysis of TCA-1 shows homology with an immunoglobulin heavy chain region, which suggests that TCA-1 may belong to the immunoglobulin supergene family of receptor and adhesion molecules.

Download Full-text

Characterization of a new T-lineage glycoprotein expressed in mature T- cell leukemias and lymphomas

Blood ◽

10.1182/blood.v75.7.1557.1557 ◽

1990 ◽

Vol 75 (7) ◽

pp. 1557-1563

Author(s):

WF Cassano

Keyword(s):

T Cell ◽

Surface Membrane ◽

Lymphocytic Leukemia ◽

Amino Acid Sequence Analysis ◽

Normal Human ◽

T Cell Malignancies ◽

Murine Monoclonal Antibodies ◽

Immunoglobulin Supergene Family ◽

Supergene Family

Abstract We identified a new human, T-lineage restricted glycoprotein of molecular weight 120 Kd that is expressed primarily in mature T-cell malignancies. The antigen, named TCA-1 (T-cell cytoplasmic antigen), is an intracellular glycoprotein found mainly in the Golgi stacks, although a few cell lines also display surface membrane TCA-1. Many but not all T-cell neoplasms express this antigen. The antigen is absent from neoplastic and normal human tissue outside the T-lymphocyte lineage. TCA-1 was identified by murine monoclonal antibodies produced after immunization of mice with T-cell chronic lymphocytic leukemia cells. The glycoprotein is a monomer containing approximately 4% N- linked carbohydrate with terminal D-galactose residues. Partial amino acid sequence analysis of TCA-1 shows homology with an immunoglobulin heavy chain region, which suggests that TCA-1 may belong to the immunoglobulin supergene family of receptor and adhesion molecules.

Download Full-text

Cytoplasmic expression of the CD3 antigen as a diagnostic marker for immature T-cell malignancies

Blood ◽

10.1182/blood.v71.3.603.bloodjournal713603 ◽

1988 ◽

Vol 71 (3) ◽

pp. 603-612

Author(s):

JJ van Dongen ◽

GW Krissansen ◽

IL Wolvers-Tettero ◽

WM Comans-Bitter ◽

HJ Adriaansen ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cell Lines ◽

Peripheral Blood ◽

Diagnostic Marker ◽

Surface Membrane ◽

Cell Lineage ◽

Normal Peripheral Blood ◽

Thymus Cell ◽

T Cell Malignancies

The expression of cytoplasmic CD3 (CyCD3) was analyzed in 45 leukemias, five thymus cell samples, five peripheral blood (PB) samples, and ten cell lines. All T cell acute lymphoblastic leukemias (T-ALL) that did not express surface membrane CD3 (SmCD3) appeared to express CyCD3. Furthermore, the majority of SmCD3+ T-ALL also expressed CyCD3. Analogous results were obtained with thymus cell samples in that about 95% of the thymocytes expressed CyCD3 whereas 60% to 75% of the thymocytes also expressed SmCD3. In normal peripheral blood only prominent SmCD3 expression was found. These data indicate that immature T cells express CyCD3 only, that the combined expression of CyCD3 and SmCD3 is characteristic for intermediate differentiation stages, and that mature T cells express prominent SmCD3. All (precursor) B cell leukemias, acute myeloid leukemias, and non-T cell lines tested did not express CyCD3. On the basis of these data, we conclude that CyCD3 expression is restricted to the T cell lineage and can be used as a diagnostic marker for immature SmCD3- T cell malignancies. Therefore, we evaluated which fixative is optimal for CyCD3 staining, and we determined by immunofluorescence staining and Western blotting which anti-CD3 monoclonal antibody (MoAb) can be used for the detection of CyCD3. In our opinion, acid ethanol was the best fixative for the cytocentrifuge preparations. Furthermore, we demonstrated that CyCD3 can be easily detected by use of MoAbs raised against denaturated CD3 chains such as those of the SP series (SP-6, SP-10, SP-64, and SP-78). In addition we tested 22 anti-CD3 MoAbs of the Oxford CD3 panel that were raised against native SmCD3, and it appeared that only four (UCHT1, VIT-3b, G19–41 and SK7/Leu-4) of them were able to detect CyCD3. In Western blot analysis all four MoAbs recognized the CD3- epsilon chain only.

Download Full-text

Characterization of normal human CD3+ CD5- and γδ T cell receptor positive T lymphocytes

Clinical & Experimental Immunology ◽

10.1111/j.1365-2249.1990.tb06450.x ◽

2008 ◽

Vol 80 (1) ◽

pp. 114-121 ◽

Cited By ~ 6

Author(s):

E. F. SROUR ◽

T. LEEMHUIS ◽

L. JENSKI ◽

R. REDMOND ◽

D. FILLAK ◽

...

Keyword(s):

T Cell ◽

T Lymphocytes ◽

T Cell Receptor ◽

Cell Receptor ◽

Γδ T Cell ◽

Normal Human ◽

Γδ T Cell Receptor

Download Full-text

An immunotoxin with therapeutic potential in T cell leukemia: WT1-ricin A

Blood ◽

10.1182/blood.v63.5.1178.1178 ◽

1984 ◽

Vol 63 (5) ◽

pp. 1178-1185 ◽

Cited By ~ 40

Author(s):

CD Myers ◽

PE Thorpe ◽

WC Ross ◽

AJ Cumber ◽

FE Katz ◽

...

Keyword(s):

T Cell ◽

Ammonium Chloride ◽

Therapeutic Potential ◽

Autologous Transplantation ◽

Lymphocytic Leukemia ◽

Normal Human ◽

A Chain ◽

Density Treatment ◽

Normal Human Bone Marrow ◽

Ricin A

Abstract A conjugate of the monoclonal antibody WT1 and ricin A-chain was studied for its suitability for purging marrow of leukemic T cells for autologous transplantation in T cell acute lymphocytic leukemia (T- ALL). The conjugate was powerfully cytotoxic to the human T-ALL cell line, GH1, which expresses the WT1 antigen at a high density. Treatment of the cells with the conjugate at 10(-11) M reduced their rate of protein synthesis by 50%, and the inclusion of 6 mM ammonium chloride in the cultures enhanced the potency of cytotoxic effect by 10–100- fold. Clonogenic assays indicated that less than 0.1% of GH1 cells survived 3-hr exposure to the conjugate in ammonium chloride. WT1 alone did not react with multipotent (CFU-GEMM) hematopoietic progenitors in normal human bone marrow, as measured by fluorescence-activated cell sorting. Under conditions giving maximal killing of GH1 cells, there was no toxicity to multipotential progenitors in normal human marrow.

Download Full-text

Generation and Characterization of a Murine Monoclonal Antibody Specific for the Human T1-Cd5 Molecule

The International Journal of Biological Markers ◽

10.1177/172460088700200302 ◽

1987 ◽

Vol 2 (3) ◽

pp. 143-150 ◽

Cited By ~ 2

Author(s):

Federico Genzano ◽

Ada Funaro ◽

Massimo Alessio ◽

Lucia B. De Monte ◽

Graziella Bellone ◽

...

Keyword(s):

Monoclonal Antibody ◽

Monoclonal Antibodies ◽

T Cell ◽

T Lymphocytes ◽

Membrane Glycoprotein ◽

Functional Features ◽

Specific Membrane ◽

Murine Monoclonal Antibodies ◽

Selection Of

Murine monoclonal antibodies (MoAbs) have found widespread applications in the characterization of the molecular and functional features of lymphocyte differentiation antigens. The present paper summarizes the results of our work dealing with the production and selection of a murine MoAb recognizing a molecule expressed during the whole differentiative life of T lymphocytes. The MoAb CB01 resulted to be specific for an apparently unique epitope of the T-cell specific membrane glycoprotein T1-CD5.

Download Full-text

T-cell receptor delta/alpha rearrangements in lymphoid neoplasms

Blood ◽

10.1182/blood.v74.3.1073.1073 ◽

1989 ◽

Vol 74 (3) ◽

pp. 1073-1083 ◽

Cited By ~ 37

Author(s):

MJ Dyer

Keyword(s):

T Cell ◽

B Cell ◽

T Cell Receptor ◽

Cell Lineage ◽

Cell Receptor ◽

Lymphocytic Leukemia ◽

Cell Precursor ◽

Lymphoid Neoplasms ◽

Histiocytic Lymphoma ◽

T Cell Malignancies

Abstract Rearrangements within the T-cell receptor (TCR)delta/alpha locus were analyzed in a wide variety of lymphoid neoplasms by eight DNA probes specific for TCR J delta, J alpha and C alpha segments. In all 11 T- cell malignancies, rearrangement and/or deletion of TCR delta was detected irrespective of the stage of maturation of the tumor. The organization of TCR delta correlated with the phenotype of the tumor: In “prethymic” T-cell acute lymphocytic leukemia (ALL), TCR delta was the only TCR gene to be rearranged. More mature T cell malignancies expressing CD4 together with CD3 showed deletion of both alleles of TCR delta, suggestive of TCR V alpha-J alpha rearrangement. All 43 B-cell tumors expressing surface immunoglobulin (sIg), including two cases of adult B-cell ALL, had germline configuration of TCR delta/alpha. In contrast, all 17 B-cell precursor ALLs (null, common, and pre-B-cell ALLs) had rearrangement and/or deletion of TCR delta/alpha. A single case of “histiocytic” lymphoma also showed biallelic deletion of TCR delta. Oligoclonal rearrangements of Ig and TCR genes were observed in two cases of B-cell precursor ALL and in one case of T-cell lymphoblastic lymphoma. Patterns of such “aberrant” TCR rearrangement were similar to those observed in T-lineage malignancies. In particular, seven of eight cases of B-cell precursor ALL and the histiocytic lymphoma which demonstrated biallelic TCR delta deletion, (suggestive of a V alpha-J alpha rearrangement) had clonal TCR beta rearrangement. These data support the hypothesis that supposedly aberrant rearrangements of the TCR genes may follow the same developmental controls as found in T-cell differentiation, despite the lack of evidence for further commitment to the T-cell lineage. TCR delta rearrangement is a useful marker of clonality of immature T-cell tumors which may have only this gene rearranged but is not specific to the T-cell lineage.

Download Full-text