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The contention that VH constitutes a part of T-cell receptors for antigens was probed by purifying rabbit T cells and analysing these cells for non-immunoglobulin VH, i.e. VH not associated with L chain. A number of anti-VH antisera were employed for this purpose, the most important being goat antiserum, reacting with common a1 allotype determinants (allotype determinants expressed on free VH and H chain as well as on intact immunoglobulins), rat antibody against common non-allotype VH determinants (VH framework determinants expressed on VH and H chain as well as on intact immunoglobulins) and chicken antibody against unmasked non-allotype determinants (VH determinants accessible only in the absence of L chain). VH and L chain was quantified by radioimmunoassays on extracts and supernatants from unstimulated T cells as well as from T cells stimulated by concanavalin A and by allogeneic cells. Absolute depletion of Ig-containing and -producing cells was not achieved but in no case was an excess of VH over L chain observed. This indicated that all detected VH originated from cells of the B lineage. The cells were also cultured in the presence of labelled amino acids followed by analysis of detergent extracts and supernatants by immunoadsorption and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) fluorography. Again, no evidence for T-cell VH could be found. Affinity purified anit-VH antibody was used to label viable rabbit T cells through the use of secondary fluorescence-labelled anti-immunoglobulin antibody. No VH-specific labelling of T cells could be observed. Mixed lymphocyte cultures were carried out in the presence of affinity-purified anti-VH antibodies. No inhibition of the reaction could be discerned. The failure to detect T-cell VH is in agreement with the recent finding that the VH-genome in T cells is not rearranged in a functional manner similar to that in B cells. 相似文献
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G. W. HOFFMANN 《Scandinavian journal of immunology》1995,41(4):331-337
An idiotypic network model of AIDS pathogenesis is described in which the T cell receptor plays a role both in infection and as a target of autoimmunity. This is an extension of a previously published autoimmunity model, and provides explanations for several otherwise puzzling aspects of AIDS pathogenesis. In the model HIV–specific T cells are preferentially infected, and HIV, acting as an antigen, stimulates the expansion of the infectable pool of T cells. The HIV variants that are most strongly selected are those that are recognized by the most helper T cells. HIV and suppressor T cells are subject to the same selective environment, and consequently undergo a process of convergent selection to resemble each other more and more with time. Eventually immunity against HIV cross–reacts with suppressor T cell idiotypes, disrupting the normal regulation of helper T cells. Autoimmunity ensues. The model leads to novel vaccine and therapy approaches involving the targeting and elimination of HIV–specific T cells. 相似文献
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The Human T Cell Receptor: Analysis with Cytotoxic T Cell Clones 总被引:20,自引:0,他引:20
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Glucosamine (GlcN), like N‐acetylglucosamine (GlcNAc), is salvaged into the hexosamine pathway and is converted to UDP‐GlcNAc. Golgi N‐glycan branching enzymes produce N‐glycans, using UDP‐GlcNAc as a substrate, which attach to the T cell receptor (TCR) and cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4). These findings suggest that GlcN exerts the immunoregulation through TCR signalling, which could be involved not only in cytokine production but also activated T cell apoptosis. In fact, a preliminary study showed that GlcN reduced the number of CD3+ T cells of NC/Nga mice with AD‐like skin lesions. Therefore, whether apoptosis of T cells would be one of the potential molecular mechanisms of GlcN‐induced immunosuppression was investigated. Cultured human primary along with Jurkat T cells and purified T cells from NC/Nga mice with or without Df‐induced AD‐like skin lesion were used for the study. Glucosamine treatment increased the number of T cells expressing β1,6GlcNAc‐branched N‐glycans, with reduced ZAP‐70 phosphorylation and enhanced CTLA‐4 expression. Glucosamine treatment reduced the number of activated T cells from both the human primary and Jurkat cells and the dermatitis‐induced mice. The expression of FasL and activated caspases, particularly caspase‐3, was increased, whereas the phosphorylation of PI3K, Akt and NF‐κB was decreased by GlcN treatment. Therefore, in addition to down‐regulating TCR signalling and promoting CTLA‐4 expression, GlcN may also suppress T cell function by enhancing apoptosis of activated T cells, through both extrinsic and intrinsic apoptotic signalling pathways, which were regulated by the inhibition of PI3K/Akt and NF‐κB phosphorylation. 相似文献
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The Structure and Function of T Cell Receptor Complexes 总被引:1,自引:0,他引:1
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The Murine T Cell Antigen Receptor and Associated Structures 总被引:5,自引:0,他引:5
James P. Allison Linda Ridge Joanne Lund Jane Gross-Pelose Lewis LanierBradley W. McIntyre 《Immunological reviews》1984,81(1):145-160
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《Biology of blood and marrow transplantation》2020,26(8):1377-1385
Adult T cell leukemia/lymphoma (ATL) is an aggressive peripheral T cell neoplasm caused by infection with human T cell lymphotropic virus type-1 (HTLV-1). Its prognosis remains extremely poor. Tax, the most important regulatory protein for HTLV-1, is associated with the aggressive proliferation of host cells and is also a major target antigen for CD8+ cytotoxic T cells (CTLs). Based on our previous findings that Tax-specific CTLs with a T cell receptor (TCR) containing a unique amino-acid sequence motif exhibit strong HLA-A*24:02-restricted, Tax301-309-specific activity against HTLV-1, we aimed to develop a Tax-redirected T cell immunotherapy for ATL. TCR-ɑ/β genes were cloned from a previously established CTL clone and transduced into peripheral blood mononuclear cells (PBMCs) of healthy volunteers using a retroviral siTCR vector. Then the cytotoxic efficacy against HTLV-1-infected T cells or primary ATL cells was assessed both in vitro and in vivo. The redirected CTLs (Tax-siCTLs) produced a large amount of cytokines and showed strong killing activity against ATL/HTLV-1-infected T cells in vitro, although they did not have universal activity against ATL cells. Next, in a xenograft mouse model using an HTLV-1-infected T cell line (MT-2), in all mice treated with Tax-siCTLs, the tumor rapidly diminished and finally disappeared without normal tissue damage, although all mice that were untreated or treated with non-gene-modified PBMCs died because of tumor progression. Our findings confirm that Tax-siCTLs can exert strong anti-ATL/HTLV-1 effects without a significant reaction against normal cells and have the potential to be a novel immunotherapy for ATL patients. 相似文献
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《International reviews of immunology》2013,32(5-6):339-363
CD4+ T cells are a major component of the inflammatory infiltrate in rheumatoid synovitis. Within synovial lesions, clonal CD4+ T cell populations are detectable, supporting the notion of an antigen specific recognition event in the joint. In general, the clonal size of individual T cell clones is small and does not lead to a marked distortion of the synovial T cell receptor (TCR) repertoire. Comparison of TCR sequences derived from different patients has not provided evidence for common sequences. Either multiple antigens are recognized or the TCR repertoire is sufficiently plastic with a multitude of different TCR structures responding to the same antigen(s). However, within one individual, the repertoire of clonal T cell populations is restricted. Identical T cell clones can be identified in different joints and at different timepoints of the disease, emphasizing that the spectrum of antigens recognized is conserved over time and that the T cell response pattern is not subject to evolution. Characterization of antigens involved in the latter stages of the disease may thus provide critical information on disease-initiating events.Recent data have led to the new concept that the role of T cells in rheumatoid arthritis (RA) is not limited to synovial inflammation. Evidence has been provided that the premorbid TCR repertoires of RA patients and normal controls can be distinguished. The T cell repertoire in RA patients is prone to recognize certain microbial products and autoantigens. The selection of this response pattern can only partially be attributed to the disease associated HLA-DRB1 alleles. Additional factors common in RA patients but not in HLA-DR matched control individuals seem to be important in shaping the TCR repertoire. Furthermore, the repertoire of mature T cells in RA patients is characterized by oligoclonality which involves T cells in the peripheral blood compartment. Possibly, these clonal T cell populations react to widespread autoantigens, raising the possibility that RA patients have a defect in controlling peripheral tolerance and an anomaly of lymphoproliferation. In contrast to joint residing CD4+T cells, expanded clonotypes isolated from the blood of different patients have been described to share TCRβ chain structures. How these characteristic features of the global TCR repertoire in RA patients translate into mechanisms of disease remains to be elucidated. 相似文献
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Genes Encoding the Human T Cell Antigen Receptor 总被引:4,自引:0,他引:4
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《Immunological investigations》2013,42(1-2):111-114
The T Vα and Vβ cell specificities repertoire usage in aging subjects was studied by the use of seven different monoclonal antibodies specific for defined regions of the T cell receptor (TCR). Except for the Vβ8subfamily, no differences were observed in the frequency of T cells bearing selected Vαβ epitopes, between old and control subjects. 相似文献
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Biochemistry and Distribution of the T Cell Receptor 总被引:2,自引:0,他引:2
Charles Hannum Johnh. Freed George Tarr John Kappler Philippa Marrack 《Immunological reviews》1984,81(1):161-176
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I-J as an Inducible T Cell Receptor for Self 总被引:4,自引:0,他引:4
"Jedenfalls, wenn man davorsteht, dann sieht man sich selbstaber eben nicht wie in einem gewöhnlichen Spiegel, versteht sich. Man sieht nicht sein Äusseres, sondern man sieht sein wahres inneres Wesen. so wie es in Wirklichkeit beschaffen ist. Wer da durch will, der muß - um es mal so auszudrücken -in sich selbst hineingehen."
Die undendliche Geschichte, bei Michael Ende, K. Thiehemanns Verlag, Stuttgart, 1979. 相似文献
Die undendliche Geschichte, bei Michael Ende, K. Thiehemanns Verlag, Stuttgart, 1979. 相似文献
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《International reviews of immunology》2013,32(5-6):323-337
Rheumatoid arthritis is a chronic and destructive autoimmune joint disease characterized by inflammation of synovial tissue of unknown aetiology. Studies on TCR genes expressed by infiltrating T cells in synovial tissues have attempted to identify mechanism and specificity of the recruitment. T cell infiltrate in rheumatoid arthritis appears to be an association of a polyclonal non specific infiltrate with dominant clones or clonotypes. T cell repertoire in synovial tissue is biased compared to peripheral blood but no TCR V gene can be identified as commonly over-used. Comparison of motifs found in the CDR3 region of dominant clones from different studies has currently failed to identified a commonly motif. The fact that a number of dominant clones or clonotypes is present in different joints and at different times of the disease suggests a selective expansion of T lymphocytes in rheumatoid arthritis synovial membrane. Further investigations are needed to characterize the specificity of these dominant clonotypes.Synovial T cell infiltrate in rheumatoid arthritis appears to be polyclonal and the majority of T cells are non-specifically recruited into sites of inflammation following tissue injury. But almost all the studies show the presence of a large number of dominant clones in the synovial tissue, using different TCR V genes, which certainly play an important role in the perpetuation of the disease. This, and the fact that a number of dominant clones or clonotypes is present in different joints and at different times of the disease, strongly suggest a selective expansion of T lymphocytes in synovial membrane. Comparison of motifs found in the CDR3 region of dominant clones from different studies is difficult as of the number of TCRs analysed is generally low and the HLA-DR differs from patient to other. To further investigate TCR in RA, identification of the pathogenic clonotypes would be the first step before characterization of CDR3 regions of dominant clonotypes. Although the target or the auto-antigens involved in the disease have not yet been identified, sequence analyses of the CDR3 regions of dominant clonotypes could, in the future, give important informations about peptides that are the targets of auto-reactive T cells. 相似文献
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Chimeric antigen receptor (CAR)-modified T cells (CAR-Ts) targeting CD19 have resulted in unprecedented durable remissions for patients with relapsed and refractory B cell malignancies. Cytokine release syndrome (CRS), resulting from rapid immune activation induced by CAR-Ts, is the most significant treatment-related toxicity. CRS initially manifests with fever and can progress to life-threatening capillary leak with hypoxia and hypotension. The clinical signs of CRS correlate with T cell activation and high levels of cytokines including IL-6. Tocilizumab, an anti-IL-6 receptor antagonist, is the standard for CRS management, but optimal timing of administration is unclear. The development of a supportive infrastructure by treatment centers is important to maintain safe administration as access expands. Collaborative efforts are underway to harmonize the definition and grading of CRS to allow for better interpretation of toxicities across CAR-T products and clinical trials and allow for informed management algorithms. 相似文献