scholarly journals Identification of shared antigenic determinants of the putative human T lymphocyte antigen receptor.

1984 ◽  
Vol 160 (2) ◽  
pp. 541-551 ◽  
Author(s):  
M B Brenner ◽  
I S Trowbridge ◽  
J McLean ◽  
J L Strominger
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Protein Complex ◽  
Antigen Receptor ◽  
Alpha Subunit ◽  
Antigenic Determinants ◽  
T Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
T Cell Lines

A mouse antiserum, anti-gp40,49 was obtained by immunizing BALB/c mice with the putative T cell antigen receptor isolated from HPB-MLT cells. This antiserum reacted with peripheral blood lymphocyte (PBL) and a panel of immunocompetent T cell lines and clones in each case precipitating from lysates of cells labeled by surface iodination, a disulfide-linked dimer consisting of an alpha subunit Mr (46,000-49,000) and a beta subunit Mr (40,000-45,000). Variability in Mr of the two subunits, particularly of the beta (light) subunit, was observed when the receptors of immunocompetent T cell lines with different antigen specificities were compared. Anti-gp40,49 serum reacted selectively with the alpha subunit after reduction and alkylation of the protein complex. These results confirm the relationship between the gp40,49 protein complex of HPB-MLT cells and the putative T cell antigen receptor on normal immunocompetent T cells and indicate that the alpha subunit of the human receptor expressed shared determinant(s) that are immunogenic in the mouse. Some features of the T cell antigen receptor appear to be unusual in that even with a xenoantiserum against the purified molecule, only antibodies against clonotypic determinants could be detected at the cell surface by quantitative immunofluorescence analysis.

scholarly journals Cooperative assembly of a four-molecule signaling complex formed upon T cell antigen receptor activation

2018 ◽  
Vol 115 (51) ◽  
pp. E11914-E11923 ◽  
Author(s):  
Asit Manna ◽  
Huaying Zhao ◽  
Junya Wada ◽  
Lakshmi Balagopalan ◽  
Harichandra D. Tagad ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
T Cell ◽  
Protein Complex ◽  
Antigen Receptor ◽  
Receptor Activation ◽  
T Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Phospholipase Cγ1 ◽  
Quaternary Complex

The T cell antigen receptor encounters foreign antigen during the immune response. Receptor engagement leads to activation of specific protein tyrosine kinases, which then phosphorylate multiple enzymes and adapter proteins. One such enzyme, phospholipase-Cγ1, is responsible for cleavage of a plasma membrane lipid substrate, a phosphoinositide, into two second messengers, diacylglycerol, which activates several enzymes including protein kinase C, and an inositol phosphate, which induces intracellular calcium elevation. In T cells, phospholipase-Cγ1 is recruited to the plasma membrane as part of a four-protein complex containing three adapter molecules. We have used recombinant proteins and synthetic phosphopeptides to reconstitute this quaternary complex in vitro. Extending biophysical tools to study concurrent interactions of the four protein components, we demonstrated the formation and determined the composition of the quaternary complex using multisignal analytical ultracentrifugation, and we characterized the thermodynamic driving forces of assembly by isothermal calorimetry. We demonstrate that the four proteins reversibly associate in a circular arrangement of binding interfaces, each protein interacting with two others. Three interactions are of high affinity, and the fourth is of low affinity, with the assembly of the quaternary complex exhibiting significant enthalpy–entropy compensation as in an entropic switch. Formation of this protein complex enables subsequent recruitment of additional molecules needed to activate phospholipase-Cγ1. Understanding the formation of this complex is fundamental to full characterization of a central pathway in T cell activation. Such knowledge is critical to developing ways in which this pathway can be selectively inhibited.

scholarly journals The T cell antigen receptor complex expressed on normal peripheral blood CD4-, CD8- T lymphocytes. A CD3-associated disulfide-linked gamma chain heterodimer.

1987 ◽  
Vol 165 (4) ◽  
pp. 1076-1094 ◽  
Author(s):  
L L Lanier ◽  
N A Federspiel ◽  
J J Ruitenberg ◽  
J H Phillips ◽  
J P Allison ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cell Lines ◽  
Peripheral Blood ◽  
Antigen Receptor ◽  
Receptor Complex ◽  
T Cell Antigen Receptor ◽  
Normal Peripheral Blood ◽  
Cell Antigen Receptor ◽  
Cell Antigen

IL-2-dependent cell lines were established from normal peripheral blood T lymphocytes that express neither CD4 nor CD8 differentiation antigens. CD3+,4-,8- cell lines from 15 different donors failed to react with WT31, an mAb directed against the T cell antigen receptor alpha/beta heterodimer. Anti-Leu-4 mAb was used to isolate the CD3/T cell antigen receptor complex from 125I-labeled CD3+,4-,8- (WT31-) T cells. Using detergent conditions that preserved the CD3/T cell antigen receptor complex, an approximately 90 kD disulfide-linked heterodimer, composed of approximately 45- and approximately 40- (or approximately 37-) kD subunits, was coimmunoprecipitated with the invariant 20-29-kD CD3 complex. Analysis of these components by nonequilibrium pH gradient electrophoresis indicated that the approximately 40-kD and approximately 37-kD subunits were similar, and quite distinct from the more basic approximately 45-kD subunit. None of these three subunits reacted with an antibody directed against a beta chain framework epitope. Heteroantiserum against a T cell receptor gamma chain peptide specifically reacted with both the approximately 37- and approximately 40-kD CD3-associated proteins, but not with the approximately 45-kD subunit. CD3+,4-,8- cells failed to transcribe substantial amounts of functional 1.3-kb beta or 1.6-kb alpha mRNA, but produced abundant 1.6-kb gamma mRNA. Southern blot analysis revealed that these CD3+,4-,8- cell lines rearranged both gamma and beta genes, and indicated that the populations were polyclonal. The expression of a CD3-associated disulfide-linked heterodimer on CD3+,4-,8- T cell lines established from normal, adult peripheral blood contrasts with prior reports describing a CD3-associated non-disulfide-linked heterodimer on CD3+/WT31- cell lines established from thymus and peripheral blood obtained from patients with immunodeficiency diseases. We propose that this discrepancy may be explained by preferential usage of the two C gamma genes in T lymphocytes.

scholarly journals Chromosome translocations involving band 7q35 or 7p15 in childhood T- cell leukemia/lymphoma

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 534-538
Author(s):  
Y Kaneko ◽  
N Maseki ◽  
C Homma ◽  
M Sakurai ◽  
S Mizutani ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Receptor ◽  
Alpha Subunit ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Subunit Gene ◽  
T Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Chromosome Translocations

In a chromosome study in childhood T-cell leukemia/lymphoma, we found t(7;11)(q35;p13) in 2 patients, t(7;14) (q35;q11) in one patient, and t(7;14)(p15;q32) in 1 patient. Southern blotting and in situ chromosomal hybridization studies in one patient with the t(7;11) demonstrated that both alleles of the T-cell antigen receptor beta- subunit gene (TCRB) were rearranged, and that one TCRB allele had relocated from 7q35 to the fusion point in band p13 of the involved chromosome 11 (11p-). These findings suggest that juxtaposition of TCRB with the putative oncogene tcl-2 located in band 11p13 may be a critical step toward development of this T-cell leukemia/lymphoma. In the other two translocations, all breakpoints were sites for lymphocyte function genes, ie, 7q35 for TCRB, 14q11 for T-cell antigen receptor alpha-subunit gene (TCRA), 7p15 for T-cell antigen receptor alpha- subunit gene (TCRG), and 14q32 for immunoglobulin heavy-chain gene (IGH). Thus, the findings in these cases allow us to expand the above hypothesis and propose that the juxtaposition of TCRB or TCRG with tcl- 2, TCRA, or IGH through chromosomal translocation may activate a mechanism for the genesis of T-cell leukemia/lymphoma with these chromosome translocations.

scholarly journals Chromosome translocations involving band 7q35 or 7p15 in childhood T- cell leukemia/lymphoma

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 534-538 ◽  
Author(s):  
Y Kaneko ◽  
N Maseki ◽  
C Homma ◽  
M Sakurai ◽  
S Mizutani ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Receptor ◽  
Alpha Subunit ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Subunit Gene ◽  
T Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Chromosome Translocations

Abstract In a chromosome study in childhood T-cell leukemia/lymphoma, we found t(7;11)(q35;p13) in 2 patients, t(7;14) (q35;q11) in one patient, and t(7;14)(p15;q32) in 1 patient. Southern blotting and in situ chromosomal hybridization studies in one patient with the t(7;11) demonstrated that both alleles of the T-cell antigen receptor beta- subunit gene (TCRB) were rearranged, and that one TCRB allele had relocated from 7q35 to the fusion point in band p13 of the involved chromosome 11 (11p-). These findings suggest that juxtaposition of TCRB with the putative oncogene tcl-2 located in band 11p13 may be a critical step toward development of this T-cell leukemia/lymphoma. In the other two translocations, all breakpoints were sites for lymphocyte function genes, ie, 7q35 for TCRB, 14q11 for T-cell antigen receptor alpha-subunit gene (TCRA), 7p15 for T-cell antigen receptor alpha- subunit gene (TCRG), and 14q32 for immunoglobulin heavy-chain gene (IGH). Thus, the findings in these cases allow us to expand the above hypothesis and propose that the juxtaposition of TCRB or TCRG with tcl- 2, TCRA, or IGH through chromosomal translocation may activate a mechanism for the genesis of T-cell leukemia/lymphoma with these chromosome translocations.

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