scholarly journals Autoaggressive myocytotoxic T lymphocytes expressing an unusual gamma/delta T cell receptor.

1992 ◽  
Vol 176 (6) ◽  
pp. 1785-1789 ◽  
Author(s):  
G Pluschke ◽  
D Rüegg ◽  
R Hohlfeld ◽  
A G Engel
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cell Clone ◽  
Cell Receptor ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
T Cell Clone ◽  
Gamma Delta T Cell

Polymyositis mediated by gamma/delta T cells is a unique disease in which autoaggressive T lymphocytes surround, invade, and destroy muscle fibers. Histochemically, the vast majority of muscle-infiltrating T cells in a patient with polymyositis were reactive with a pan-gamma/delta T cell receptor (TCR)-specific monoclonal antibody (TCR-delta 1+), but unlike > 90% of peripheral blood gamma/delta T cells, these lymphocytes did not react with V delta 1- or V gamma 9-specific antibodies (A13- and Ti gamma A-, respectively). Differential reactivity with two different V delta 2-specific monoclonal antibodies (BB3-/TiV-delta 2+) indicated that the infiltrating T cells express a V delta 2-containing TCR with unusual additional structural features. Using conventional and anchored polymerase chain reaction for the analysis of TCR transcripts, we found a striking predominance of one unusual V delta 2-J delta 3 recombination and one V gamma 3-J gamma 1 recombination. Both the unusual phenotype (TCR-delta 1+/A13-/Ti gamma A-/BB3-/TiV-delta 2+) and the dominance of distinct TCR transcripts are compatible with the assumption that one T cell clone, which expresses a V gamma 3-J gamma 1-C gamma 2/V delta 2-J delta 3-C delta disulfide-linked TCR, dominates among the infiltrating T cells of the polymyositis muscle specimen analyzed.

scholarly journals Amino acid substitutions in the floor of the putative antigen-binding site of H-2T22 affect recognition by a gamma delta T-cell receptor

1993 ◽  
Vol 90 (23) ◽  
pp. 11396-11400 ◽  
Author(s):  
S Moriwaki ◽  
B S Korn ◽  
Y Ichikawa ◽  
L van Kaer ◽  
S Tonegawa
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Peptide Transporter ◽  
Affect Recognition ◽  
Antigen Binding ◽  
In Vitro Mutagenesis ◽  
Gamma Delta ◽  
T Cell Clone ◽  
Gamma Delta T Cell

We have previously identified a self-reactive gamma delta T-cell clone (KN6) specific for the H-2T region gene product T22b. Now we have investigated by an in vitro mutagenesis analysis of the T22b gene the possibility that the interaction between the KN6 gamma delta T-cell receptor and T22b involves a peptide. The results demonstrate that mutations at the floor of the putative antigen-binding groove of T22b affect recognition by the gamma delta T-cell receptor. Furthermore, we have shown that KN6 cells react with cells that are deficient in the class I peptide transporter TAP1/TAP2. These results suggest that peptide is involved in the interaction of the KN6 T-cell receptor with T22 and that loading of T22 with the putative peptide is TAP1/TAP2-independent.

scholarly journals An invariant V alpha 24-J alpha Q/V beta 11 T cell receptor is expressed in all individuals by clonally expanded CD4-8- T cells.

1994 ◽  
Vol 180 (3) ◽  
pp. 1171-1176 ◽  
Author(s):  
P Dellabona ◽  
E Padovan ◽  
G Casorati ◽  
M Brockhaus ◽  
A Lanzavecchia
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Clone ◽  
Cell Subset ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
T Cell Clone ◽  
Gene Usage ◽  
Beta Gene

The T cell receptor (TCR)-alpha/beta CD4-8- (double negative, DN) T cell subset is characterized by an oligoclonal repertoire and a restricted V gene usage. By immunizing mice with a DN T cell clone we generated two monoclonal antibodies (mAbs) against V alpha 24 and V beta 11, which have been reported to be preferentially expressed in DN T cells. Using these antibodies, we could investigate the expression and pairing of these V alpha and V beta gene products among different T cell subsets. V alpha 24 is rarely expressed among CD4+ and especially CD8+ T cells. In these cases it is rearranged to different J alpha segments, carries N nucleotides, and pairs with different V beta. Remarkably, V alpha 24 is frequently expressed among DN T cells and is always present as an invariant rearrangement with J alpha Q, without N region diversity. This invariant V alpha 24 chain is always paired to V beta 11. This unique V alpha 24-J alpha Q/V beta 11 TCR was found in expanded DN clones from all the individuals tested. These findings suggest that the frequent occurrence of cells carrying this invariant TCR is due to peripheral expansion of rare clones after recognition of a nonpolymorphic ligand.

T-cell receptor repertoire of circulating gamma delta T-cells in Takayasu's arteritis

2006 ◽  
Vol 118 (2-3) ◽  
pp. 243-249 ◽  
Author(s):  
Sunil Kumar Chauhan ◽  
Naresh Kumar Tripathy ◽  
Nakul Sinha ◽  
Soniya Nityanand
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Takayasu’S Arteritis ◽  
Cell Receptor ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Receptor Repertoire ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

scholarly journals Novel primary thymic defect with T lymphocytes expressing gamma delta T cell receptor.

1989 ◽  
Vol 42 (7) ◽  
pp. 705-711 ◽  
Author(s):  
C Geisler ◽  
G Pallesen ◽  
P Platz ◽  
N Odum ◽  
E Dickmeiss ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Gamma Delta ◽  
Gamma Delta T Cell

Generating of Human CD4+ and CD8+ T Lymphocytes toward NY-ESO-1 by T Cell Receptor (TCR) Modification and Transduction for Adoptive TCR Gene-Transfer

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3533-3533
Author(s):  
Holger Krönig ◽  
Kathrin Hofer ◽  
Daniel Sommermeyer ◽  
Christian Peschel ◽  
Wolfgang Uckert ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Gene Transfer ◽  
T Cell Receptor ◽  
Cell Clone ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Cell Clones ◽  
T Cell Clone ◽  
T Cell Transfer

Abstract The Cancer Testis (CT) antigen NY-ESO-1 is one of the most immunogenic cancer antigens eliciting strong humoral and cellular immune responses in tumor patients and therefore it is a promising candidate antigen for successful adoptive T cell transfer. The aim of our studies is the transfer of autologous T cells re-directed towards CT antigens by T cell receptor (TCR) gene transfer. The first precondition for genetic transfer of CT-Ag-specific TCRs is the availability of tumor-reactive CD4+ and CD8+ T cell clones that express a CT-Ag-specific TCR. Therefore, we generated the autologous CD8+ T cell clone ThP2 through stimulating HLA-A2.1− PBMCs with autologous HLA-A2+DCs loaded with synthetic NY-ESO-1157–165. After two restimulations, FACS-sorting and cloning, the T cell line specifically recognized the NY-ESO-1157–165 peptide and also specifically lysed NY-ESO-1157–165 expressing tumor cells. In addition, we generated NY-ESO-1 specific T helper1 clones from HLA-DR1+ and HLA-DR4+ healthy donors by stimulation of CD4+ T cells with autologous dendritic cells (DC) pulsed with the NY-ESO-187–111 peptide. The specificity of CD4+ T helper cell clones was determined by proliferation assays and IFN gamma ELISPOT through screening with the NY-ESO-187–111 peptide. By limiting dilution of the NYESO- 1-specific T cell populations we succeeded to isolate CD4+ T cell clones, which recognized NY-ESO-1-pulsed target cells and DCs pulsed with NY-ESO-1 protein. The second precondition for TCR gene transfer is the availability of efficient vector systems. Using vectors based upon mouse myelo-proliferative sarcoma virus (MPSV), it was possible to achieve a high transgene expression in the TCR-transduced T cells. Therefore, we cloned the TCR of the HL-A2-restricted NY-ESO-1-specific CTL clone ThP2 in the retroviral vector and documented the correct expression of the TCR-chains using peptide/HLA-multimers following retroviral transduction of peripheral PBMCs. Moreover, the NY-ESO-1 specific lysis of HLA-A2+ NY-ESO-1+ tumor cell lines after transduction in primary T cells was as well effective as the primary T cell clone. Because the expression of naive transgenic T cell receptors in recipient human T cells is often insufficient to achieve highly reactive T cell bulks we modified the TCR of the ThP2 CTL clone by, murinisation, codon optimalization or by introducing cysteins into the constant regions. Afterwards we compared the expression efficiency of the three different modifications on naive T cells by tetramer-staining. We were able to show that codon optimalization leads to an increase in the expression levels of the transgenic TCRs in human CD8+ T cells. The next step is the development of T cell transfer regiments, which are based on class-II-restricted TCR-transduced T cells.

scholarly journals Fetal liver T cell receptor gamma/delta+ T cells as cytotoxic T lymphocytes specific for maternal alloantigens.

1992 ◽  
Vol 176 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Y Miyagawa ◽  
T Matsuoka ◽  
A Baba ◽  
T Nakamura ◽  
T Tsuno ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Lines ◽  
Fetal Liver ◽  
Cell Receptor ◽  
Lymphoid Cells ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Killer Activity

We have established fetal liver-derived T cell receptor (TCR) gamma/delta+, CD3+ T cell lines that are cytotoxic for maternal T cells. Fetal liver-derived lymphoid progenitors yielded predominantly TCR-gamma/delta+ cell clusters when cultured on fetal bone marrow-derived stromal cells in the presence of a cytokine cocktail under magnetic force. These tightly adherent clusters were cloned by limiting dilution and the resulting cell lines analyzed for phenotype and function. Six of eight TCR-gamma/delta lines from 8-9.5-wk gestation fetuses were V delta 2+ as compared with zero of eight lines from later stages of gestation (10 and 15 wk), where all the lines were V delta 1+. In cytotoxicity assays, these TCR-gamma/delta+, CD3+, CD4-, and CD8+ or CD8- long-term cultured lymphoid cells (LLC) were killer cells active against the class I antigens on maternal T cells. Of the cell lines, the CD8+ TCR-gamma/delta+ LLC had the highest levels of killer activity. Thus fetal liver TCR-gamma/delta+ T cells may play a crucial role in protection against invading maternal T cells generated in the feto-maternal interaction.

scholarly journals gamma/delta T cell-deficient mice have impaired mucosal immunoglobulin A responses.

1996 ◽  
Vol 183 (4) ◽  
pp. 1929-1935 ◽  
Author(s):  
K Fujihashi ◽  
J R McGhee ◽  
M N Kweon ◽  
M D Cooper ◽  
S Tonegawa ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cholera Toxin ◽  
T Cell Receptor ◽  
Tetanus Toxoid ◽  
Plasma Cells ◽  
Cell Receptor ◽  
Gamma Delta ◽  
Igg Antibody ◽  
Gamma Delta T Cell

Mucosal tissues of mice are enriched in T cells that express the gamma/delta T cell receptor. Since the function of these cells remains unclear, we have compared mucosal immune responses in gamma/delta T cell receptor-deficient (TCRdelta-/-) mice versus control mice of the same genetic background. The frequency of intestinal immunoglobulin (Ig) A plasma cells as well as IgA levels in serum, bile, saliva, and fecal samples were markedly reduced in TCRdelta-/- mice. The TCRdelta-/- mice produced much lower levels of IgA antibodies when immunized orally with a vaccine of tetanus toxoid plus cholera toxin as adjuvant. Conversely, the antigen-specific IgM and IgG antibody responses were comparable to orally immunized control mice. Direct assessment of the cells forming antibodies against the tetanus toxoid and cholera toxin antigens indicated that significantly lower numbers of IgA antibody-producing cells were present in the intestinal lamina propria and Peyer's patches of TCRdelta-/- mice compared with the orally immunized control mice. The selective reduction of IgA responses to ingested antigens in the absence of gamma/delta T cells suggests a specialized role for gamma/delta cells in mucosal immunity.

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