Expression of Two T Cell Receptor α Chains: Dual Receptor T Cells

Padovan, Elisabetta; Casorati, Giulia; Dellabona, Paolo; Meyer, Stefan; Brockhaus, Manfred; Lanzavecchia, Antonio

doi:10.1126/science.8211163

Cited by 486 publications

(375 citation statements)

References 14 publications

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“…The increase was alloantigen specific as there was no difference in the frequency of third party SJL-reactive T cells between groups. It is notable that the spleen cells of naïve animals have a low but detectable frequency of donor-reactive IFN-g-producing cells, suggesting that these cells were primed by cross-reactive environmental antigens or that they express two T cell receptors (TCRs) (26). B10.A heart graft rejection also resulted in an increase in the frequency of IFN-g-producing T cells specific for I-Ap and for B10.A sonicates (but not third party SJL sonicates) compared with T cells from naïve mice (no detectable indirect response was noted in naïve animals), demonstrating anticipated priming through the indirect pathway ( Figure 2).…”

Section: Memory T Cells Abrogate Prolonged Graft Survivalmentioning

confidence: 99%

Primed Allospecific T Cells Prevent the Effects of Costimulatory Blockade on Prolonged Cardiac Allograft Survival in Mice

Valujskikh

Pantenburg

Heeger

2002

American Journal of Transplantation

229

214

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Section: Memory T Cells Abrogate Prolonged Graft Survivalmentioning

confidence: 99%

Primed Allospecific T Cells Prevent the Effects of Costimulatory Blockade on Prolonged Cardiac Allograft Survival in Mice

Valujskikh

Pantenburg

Heeger

2002

American Journal of Transplantation

229

214

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“…Findings from other laboratories have estimated that 7-29% of peripheral T lymphocytes express two TCR ␣-chains (23,50), and this mechanism is one way for potentially autoreactive CTL to exist in the periphery and remain tolerant to self (22,24). To examine the possibility that K d HA-specific CTL in InsHA mice were using this mechanism to down-regulate avidity to HA, it was necessary to perform analysis of InsHA CTL at the single cell level.…”

Section: Isolation and Characterization Of K D Ha-specific Insha And mentioning

confidence: 99%

“…However, other mechanisms exist that can down-regulate the avidity of a T lymphocyte for cognate Ag. A CD8 ϩ lymphocyte with a high affinity TCR for self can escape deletion by decreasing cell surface expression of the TCR (8,20,21) or by expressing a second TCR ␣-chain (22)(23)(24)(25)(26). This results in decreased expression of the potentially autoimmune TCR ␣/␤ heterodimer, which spares the cell from thymic or peripheral elimination.…”

mentioning

confidence: 99%

Characterization of CD8+ T Lymphocytes That Persist After Peripheral Tolerance to a Self Antigen Expressed in the Pancreas

Nugent

Morgan

Biggs

et al. 2000

The Journal of Immunology

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As a result of expression of the influenza hemagglutinin (HA) in the pancreatic islets, the repertoire of HA-specific CD8+ T lymphocytes in InsHA transgenic mice (D2 mice expressing the HA transgene under control of the rat insulin promoter) is comprised of cells that are less responsive to cognate Ag than are HA-specific CD8+ T lymphocytes from conventional mice. Previous studies of tolerance induction involving TCR transgenic T lymphocytes suggested that a variety of different mechanisms can reduce avidity for Ag, including altered cell surface expression of molecules involved in Ag recognition and a deficiency in signaling through the TCR complex. To determine which, if any, of these mechanisms pertain to CD8+ T lymphocytes within a conventional repertoire, HA-specific CD8+ T lymphocytes from B10.D2 mice and B10.D2 InsHA transgenic mice were compared with respect to expression of cell surface molecules, TCR gene utilization, binding of tetrameric KdHA complexes, lytic mechanisms, and diabetogenic potential. No evidence was found for reduced expression of TCR or CD8 by InsHA-derived CTL, nor was there evidence for a defect in triggering lytic activity. However, avidity differences between CD8+ clones correlated with their ability to bind KdHA tetramers. These results argue that most of the KdHA-specific T lymphocytes in InsHA mice are not intrinsically different from KdHA-specific T lymphocytes isolated from conventional animals. They simply express TCRs that are less avid in their binding to KdHA.

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“…Rearranged T cells express only a single type of variable β-(VB) chain and, therefore, its CDR3 region, that most directly engages the peptide presented within human leukocyte antigen-groove, can serve as a marker of clonal expansion (clonotype) [14,15]. Clonal CTL expansion results in the overrepresentation of the respective TCR VB chain and the molecular analysis of the TCR repertoire can reveal the clonotypic structure of expanded T cell.…”

Section: Materials and Methods-using Rational Algorithms For T-cell Rmentioning

confidence: 99%

Clonal predominance of CD8+ T cells in patients with unexplained neutropenia

Wlodarski

Nearman

Jiang

et al. 2008

Experimental Hematology

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Objective-T-cell-mediated autoimmunity may be involved in some cases of idiopathic neutropenia. We hypothesized that a precise T-cell receptor repertoire analysis may uncover cytotoxic T-cell (CTL) expansions that are less pronounced than those seen in T large granular lymphocyte leukemia (T-LGL), but are pathophysiologically analogous and thus can serve as markers of a T-cell-mediated process. Materials and Methods-Using rational algorithms for T-cell receptor analysis and in vivotracking of CTL responses previously established in our laboratory, we studied patients with unexplained chronic neutropenia (n = 20), T-LGL (n = 15), and healthy controls (n = 12). We further investigated the involvement of soluble inhibitory factors by coculture assays. To determine the level of immune activation, we studied interferon-g expression in CD8 + cells using Taqman polymerase chain reaction.Results-Fifteen expanded (immunodominant) CTL clones were detected in 12 of 20 patients. In comparison to LGL leukemia, these clones were less immunodominant, but clearly discernible from subclinical lymphoproliferations in controls. As a surrogate of cytotoxic activity, we found markedly increased production of interferon-γ in most of the neutropenia patients, irrespective of the presence of immunodominant CTL clones.Conclusions-These results suggest that, while immunodominant CTL clones are detectable in a proportion of patients only, CTL-mediated pathophysiology may be a general mechanism operating in idiopathic neutropenia. Oligogoclonal CTL expansions in chronic neutropenia may indicate an ongoing autoimmune process, while highly polarized monoclonalities in a subset of neutropenic LGL patients may represent the "extreme" end of the clonal continuum.Drugs, hereditary factors, infections, and intrinsic bone marrow diseases explain the etiology of most neutropenias. The inability to detect an immune-mediated process or other obvious cause often leads to diagnosis of chronic idiopathic neutropenia (CIN) [1][2][3][4][5][6]. Similarly, secondary autoimmune neutropenia (AIN), usually associated with collagen vascular diseases, lymphoproliferative disorders and viruses, is typically diagnosed by exclusion and thus relies on the quality of clinical and laboratory workups [6][7][8][9]. Lineage-restricted cytopenias, including neutropenia, have been associated with T-cell large granular lymphocyte leukemia It is likely that patients with AIN/CIN may belong to a heterogeneous group of diseases combining various autoimmune etiologies. Appearance of the bone marrow may reveal some clues as to the cellular targets of the autoimmune process; left shift could indicate that more mature cells are targets, while pure white cell aplasia suggests that very early myeloid precursors are affected. The similar target spectrum in AIN/CIN and T-LGL suggests that cytotoxic T-cell (CTL)-mediated autoimmunity can also operate in AIN/CIN. Consequently, detection of highly polarized CTL expansions in some cases of neutropenia patients may be consistent wi...

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Expression of Two T Cell Receptor α Chains: Dual Receptor T Cells

Cited by 486 publications

References 14 publications

Primed Allospecific T Cells Prevent the Effects of Costimulatory Blockade on Prolonged Cardiac Allograft Survival in Mice

Primed Allospecific T Cells Prevent the Effects of Costimulatory Blockade on Prolonged Cardiac Allograft Survival in Mice

Characterization of CD8+ T Lymphocytes That Persist After Peripheral Tolerance to a Self Antigen Expressed in the Pancreas

Clonal predominance of CD8+ T cells in patients with unexplained neutropenia

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