Protein Phosphatase 2A Isotypes Regulate Cell Surface Expression of the T Cell Receptor

2001 ◽  
Vol 18 (1) ◽  
pp. 24-33 ◽  
Author(s):  
Jens Peter H. Lauritsen ◽  
Charlotte Menné ◽  
Jesper Kastrup ◽  
Jes Dietrich ◽  
Carsten Geisler
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
T Cell Receptor ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Cell Receptor ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Phosphatase 2A

Engagement of the CD4 molecule influences cell surface expression of the T-cell receptor on thymocytes

Nature ◽  
1988 ◽  
Vol 336 (6194) ◽  
pp. 76-79 ◽  
Author(s):  
Susan A. McCarthy ◽  
Ada M. Kruisbeek ◽  
Ingeborg K. Uppenkamp ◽  
Susan O. Sharrow ◽  
Alfred Singer
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Surface Expression ◽  
Cell Surface Expression

scholarly journals Allelic Exclusion in pTα-deficient Mice: No Evidence for Cell Surface Expression of Two T Cell Receptor (TCR)-β Chains, but Less Efficient Inhibition of Endogeneous Vβ→ (D)Jβ Rearrangements in the Presence of a Functional TCR-β Transgene

1997 ◽  
Vol 186 (5) ◽  
pp. 767-775 ◽  
Author(s):  
Anna Krotkova ◽  
Harald von Boehmer ◽  
Hans Jörg Fehling
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Allelic Exclusion ◽  
Thymocyte Development ◽  
Β Chain ◽  
Deficient Mice

Although individual T lymphocytes have the potential to generate two distinct T cell receptor (TCR)-β chains, they usually express only one allele, a phenomenon termed allelic exclusion. Expression of a functional TCR-β chain during early T cell development leads to the formation of a pre-T cell receptor (pre-TCR) complex and, at the same developmental stage, arrest of further TCR-β rearrangements, suggesting a role of the pre-TCR in mediating allelic exclusion. To investigate the potential link between pre-TCR formation and inhibition of further TCR-β rearrangements, we have studied the efficiency of allelic exclusion in mice lacking the pre-TCR-α (pTα) chain, a core component of the pre-TCR. Staining of CD3+ thymocytes and lymph node cells with antibodies specific for Vβ6 or Vβ8 and a pool of antibodies specific for most other Vβ elements, did not reveal any violation of allelic exclusion at the level of cell surface expression. This was also true for pTα-deficient mice expressing a functionally rearranged TCR-β transgene. Interestingly, although the transgenic TCR-β chain significantly influenced thymocyte development even in the absence of pTα, it was not able to inhibit fully endogeneous TCR-β rearrangements either in total thymocytes or in sorted CD25+ pre-T cells of pTα−/− mice, clearly indicating an involvement of the pre-TCR in allelic exclusion.

scholarly journals The Protein Phosphatase 2A Regulatory Subunit B56γ Mediates Suppression of T Cell Receptor (TCR)-induced Nuclear Factor-κB (NF-κB) Activity

2014 ◽  
Vol 289 (21) ◽  
pp. 14996-15004 ◽  
Author(s):  
Rebecca Breuer ◽  
Michael S. Becker ◽  
Markus Brechmann ◽  
Thomas Mock ◽  
Rüdiger Arnold ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Regulatory Subunit ◽  
Nuclear Factor ◽  
Phosphatase 2A

scholarly journals Fc gamma RII/III and CD2 expression mark distinct subpopulations of immature CD4-CD8- murine thymocytes: in vivo developmental kinetics and T cell receptor beta chain rearrangement status.

1993 ◽  
Vol 177 (4) ◽  
pp. 1079-1092 ◽  
Author(s):  
H R Rodewald ◽  
K Awad ◽  
P Moingeon ◽  
L D'Adamio ◽  
D Rabinowitz ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Fetal Development ◽  
Cell Receptor ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Immunoglobulin Gene ◽  
Beta Chain ◽  
Double Positive ◽  
Alpha Beta

We have recently identified a dominant wave of CD4-CD8- (double-negative [DN]) thymocytes in early murine fetal development that express low affinity Fc gamma receptors (Fc gamma RII/III) and contain precursors for Ti alpha/beta lineage T cells. Here we show that Fc gamma RII/III is expressed in very immature CD4low single-positive (SP) thymocytes and that Fc gamma RII/III expression is downregulated within the DN subpopulation and before the CD3-CD8low SP stage in T cell receptor (TCR)-alpha/beta lineage-committed thymocytes. DN Fc gamma RII/III+ thymocytes also contain a small fraction of TCR-gamma/delta lineage cells in addition to TCR-alpha/beta progenitors. Fetal day 15.5 DN TCR-alpha/beta lineage progenitors can be subdivided into three major subpopulations as characterized by cell surface expression of Fc gamma RII/III vs. CD2 (Fc gamma RII/III+CD2-, Fc gamma RII/III+CD2+, Fc gamma RII/III-CD2+). Phenotypic analysis during fetal development as well as adoptive transfer of isolated fetal thymocyte subpopulations derived from C57B1/6 (Ly5.1) mice into normal, nonirradiated Ly5.2 congenic recipient mice identifies one early differentiation sequence (Fc gamma RII/III+CD2(-)-->Fc gamma RII/III+CD2(+)-->Fc gamma RII/III-CD2+) that precedes the entry of DN thymocytes into the CD4+CD8+ double-positive (DP) TCRlow/- stage. Unseparated day 15.5 fetal thymocytes develop into DP thymocytes within 2.5 d and remain at the DP stage for > 48 h before being selected into either CD4+ or CD8+ SP thymocytes. In contrast, Fc gamma RII/III+CD2- DN thymocytes follow this same developmental pathway but are delayed by approximately 24 h before entering the DP compartment, while Fc gamma RII/III-CD2+ display accelerated development by approximately 24 h compared with total day 15.5 thymocytes. Fc gamma RII/III-CD2+ are also more developmentally advanced than Fc gamma RII/III+CD2- fetal thymocytes with respect to their TCR beta chain V(D)J rearrangement. At day 15.5 in gestation, beta chain V(D)J rearrangement is mostly, if not entirely, restricted to the Fc gamma RII/III-CD2+ subset of DN fetal thymocytes. Consistent with this analysis in fetal thymocytes, > 90% of adult thymocytes derived from mice carrying a disrupting mutation at the recombination-activating gene 2 locus (RAG-2-/-) on both alleles are developmentally arrested at the DN CD2- stage. In addition, there is a fivefold increase in the relative percentage of thymocytes expressing Fc gamma RII/III in TCR and immunoglobulin gene rearrangement-incompetent homozygous RAG-2-/- mice (15% Fc gamma RII/III+) versus rearrangement-competent heterozygous RAG-2+/- mice (< 3% Fc gamma RII/III+). Thus, Fc gamma RII/III expression defines an early DN stage preceding V beta(D beta)I beta rearrangement, which in turn is followed by surface expression of CD2. Loss of Fc gamma RII/III and acquisition of CD2 expression characterize a late DN stage immediately before the conversion into DP thymocytes.

Defective synthesis or association of T-cell receptor chains underlies loss of surface T-cell receptor–CD3 expression in enteropathy-associated T-cell lymphoma

Blood ◽  
2008 ◽  
Vol 112 (13) ◽  
pp. 5103-5110 ◽  
Author(s):  
Jennifer M. L. Tjon ◽  
Wieke H. M. Verbeek ◽  
Yvonne M. C. Kooy-Winkelaar ◽  
Binh H. Nguyen ◽  
Arno R. van der Slik ◽  
...  
Keyword(s):  
Celiac Disease ◽  
T Cell ◽  
Cell Surface ◽  
Cell Line ◽  
T Cell Receptor ◽  
Cell Lymphoma ◽  
Cell Receptor ◽  
Intraepithelial Lymphocytes ◽  
T Cell Lymphoma ◽  
Cell Surface Expression

Abstract Enteropathy-associated T-cell lymphoma, an often fatal complication of celiac disease, can result from expansion of aberrant intraepithelial lymphocytes in refractory celiac disease type II (RCD II). Aberrant intraepithelial lymphocytes and lymphoma cells are intracellularly CD3ϵ+ but lack expression of the T-cell receptor (TCR)–CD3 complex on the cell surface. It is unknown what causes the loss of TCR-CD3 expression. We report the isolation of a cell line from an RCD II patient with the characteristic phenotype of enteropathy-associated T-cell lymphoma. We demonstrate that in this cell line the TCR-α and -β chains as well as the CD3γ, CD3δ, CD3ϵ, and ζ-chains are present intracellularly and that assembly of the CD3γϵ, CD3δϵ, and ζζ-dimers is normal. However, dimerization of the TCR chains and proper assembly of the TCR-CD3 complex are defective. On introduction of exogenous TCR-β chains, but not of TCR-α chains, assembly and functional cell surface expression of the TCR-CD3 complex were restored. Defective synthesis of both TCR chains was found to underlie loss of TCR expression in similar cell lines isolated from 2 additional patients. (Pre)malignant transformation in RCD II thus correlates with defective synthesis or defective association of the TCR chains, resulting in loss of surface TCR-CD3 expression.

scholarly journals Expression and function of a variant T cell receptor complex lacking CD3-gamma.

1991 ◽  
Vol 174 (2) ◽  
pp. 319-326 ◽  
Author(s):  
P Pérez-Aciego ◽  
B Alarcón ◽  
A Arnaiz-Villena ◽  
C Terhorst ◽  
M Timón ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Surface Expression ◽  
Calcium Flux ◽  
Cell Surface Expression ◽  
Receptor Complex ◽  
T Cell Lines ◽  
And Function ◽  
Zeta Chains

A T cell line termed DIL2 has been derived from an infant with a polyclonal T cell receptor (TCR)/CD3 cell surface expression defect. Indirect immunofluorescence showed that the expression of certain TCR/CD3 epitopes (like those detected by WT31 and BMA031 monoclonals) was strongly reduced (around five-fold) on DIL2, whereas other epitopes (like those detected by SP34 and Leu4) were only around two-fold lower than in normal T cell lines. Specific immunoprecipitates of surface-radioiodinated DIL2 cells contained TCR-alpha, TCR-beta, CD3-delta, CD3-epsilon and TCR-zeta chains, but lacked CD3-gamma. This structural TCR/CD3 variant was, however, capable of transducing certain activation signals, since normal proliferation and a low but significant calcium flux was observed in DIL2 cells after engagement with specific antibodies. Our data suggest that a functional TCR/CD3 complex can be expressed on the surface of T cells in the absence of CD3-gamma.

scholarly journals Surface expression of only gamma delta and/or alpha beta T cell receptor heterodimers by cells with four (alpha, beta, gamma, delta) functional receptor chains.

1988 ◽  
Vol 168 (3) ◽  
pp. 1003-1020 ◽  
Author(s):  
T Saito ◽  
F Hochstenbach ◽  
S Marusic-Galesic ◽  
A M Kruisbeek ◽  
M Brenner ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Surface Expression ◽  
Gamma Delta ◽  
Stringent Control ◽  
Repertoire Diversity ◽  
Alpha Beta ◽  
Functional Receptor

Surface expression of TCR dimers by cells synthesizing three or four distinct types of receptor chains was analyzed. Cells containing intact gamma, alpha, and beta chains had only gamma delta dimers on the cell surface. In human PEER cells, addition of a functional alpha chain led to the loss of gamma delta dimer expression and expression of only alpha beta dimers. This result was not due to transcriptional down-regulation of the gamma or delta loci. In murine cells expressing all four chains, both gamma delta and alpha beta dimers could be demonstrated on a single cell. No other chain combinations (alpha gamma, alpha delta, beta gamma, or beta delta) were detected. Thus, there is stringent control of assembly and/or transport of TCR heterodimers, such that functional receptors consist only of alpha beta and gamma delta pairs, and no additional repertoire diversity is generated by cross pairing.

Efficiency of T-cell receptor expression in dual-specific T cells is controlled by the intrinsic qualities of the TCR chains within the TCR-CD3 complex

Blood ◽  
2006 ◽  
Vol 109 (1) ◽  
pp. 235-243 ◽  
Author(s):  
Mirjam H. M. Heemskerk ◽  
Renate S. Hagedoorn ◽  
Menno A. W. G. van der Hoorn ◽  
Lars T. van der Veken ◽  
Manja Hoogeboom ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Surface ◽  
Viral Infections ◽  
Cell Receptor ◽  
Surface Expression ◽  
Receptor Expression ◽  
Leukemic Cells ◽  
Cell Surface Expression ◽  
Cell Immunity

Abstract Genetic engineering of T lymphocytes is an attractive strategy to specifically redirect T-cell immunity toward viral infections and malignancies. We previously demonstrated redirected antileukemic reactivity of cytomegalovirus (CMV)–specific T cells by transfer of minor histocompatibility antigen HA-2–specific T-cell receptors (TCRs). HA-2–TCR-transferred CMV-specific T cells were potent effectors against HA-2–expressing leukemic cells, as well as CMV-expressing cells. Functional activity of these T cells correlated with TCR cell-surface expression. In the present study we analyzed which properties of transferred and endogenous TCRs are crucial for efficient cell-surface expression. We demonstrate that expression of the introduced TCR is not a random process but is determined by characteristics of both the introduced and the endogenously expressed TCR. The efficiency of TCR cell-surface expression is controlled by the intrinsic quality of the TCR complex. In addition, we demonstrate that chimeric TCRs can be formed and that efficiency of TCR expression is independent of whether TCRs are retrovirally introduced or naturally expressed. In conclusion, introduced, endogenous, and chimeric TCRs compete for cell-surface expression in favor of the TCR-CD3 complex with best-pairing properties.

Surface programmable activation receptor (SPAR) cell platform for the rapid detection of melanoma-specific biomarkers.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14263-e14263
Author(s):  
Joel Lwande ◽  
Joseph D Kittle ◽  
M. Russell Williams ◽  
Shengwen Liang ◽  
Kyle McQuaid ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
T Cell Receptor ◽  
Target Detection ◽  
Cell Activation ◽  
Cell Receptor ◽  
Jurkat Cells ◽  
Cell Surface Expression ◽  
Specific Cell ◽  
Luminescent Signal

e14263 Background: We have previously demonstrated that SPAR modified T cells effectively detect bacterial and viral pathogens. SPAR cells are engineered to express a modified T cell receptor (TCR) capable of antibody-directed signal transduction and respond with a Ca2+-mediated production of luminescent signal upon target detection. Here we describe the ability of SPAR cells to rapidly detect the cell surface expression of melanoma biomarkers without a requirement for extensive sample preparation. Methods: SPAR cells expressing both an engineered T cell receptor and the luminescent reporter protein aequorin were developed via the transfection of Jurkat cells with the aequorin expression vector pEF1-Aeq and an engineered TCR complex composed of mouse FcγRI fused to the CD3ζ subunit. The mFcγRI-CD3ζ receptor binds to the Fc region of full-length mouse IgG2 antibodies: SPAR cells are programmed for target detection via the addition of target-specific antibody. The ability of programmed SPAR cells to accurately detect melanoma-specific cell surface biomarkers was evaluated using whole cells from cultured mouse (B16-F10) and human (SK-Mel-28) melanoma cell lines. SPAR cells were programmed by incubation with murine antibodies directed toward the melanoma biomarkers CD133 or TRP1, then mixed with melanoma cells or K562 control cells and evaluated for signal generation. Results: SPAR cells programmed with anti-CD133 or anti-TRP1 antibody produced luminescent signal within minutes when combined with human SK-Mel-28 cells or mouse B16-F10 cells, respectively, known to abundantly express the appropriate biomarker. No signal was generated when programmed SPAR cells were incubated with K562 cells. Further studies also document cytokine production following receptor engagement. Conclusions: SPAR cells can be programmed for the rapid and specific detection of known cell surface cancer biomarkers. The Ca2+-dependent production of luminescent signal and cytokine release in response to TCR engagement suggests SPAR cell activation. Thus, in addition to biomarker detection the SPAR system may ultimately provide predictive insights into the potency of antibody-directed cell therapy.

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