Mitogens, superantigens, and nominal antigens elicit distinctive patterns of TCRB CDR3 diversity

Currier, Jeffrey R.; Deulofeut, Harold; Barron, Karyl S.; Kehn, P J; Robinson, Mary Ann

doi:10.1016/0198-8859(96)00076-6

Cited by 65 publications

(42 citation statements)

References 26 publications

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“…10, which is published as supporting information on the PNAS web site). Representative analysis of the V␣14 and V␤14 CDR3 spectratypes revealed Gaussian and skewed (V␤14 Neutrophils 1) CDR3 length distribution profiles indicative of complex V␣␤ repertoires as they are observed in T cells (12). TCR V␣␤ expression profiles in neutrophils differed interindividually ( Fig.…”

Section: Resultsmentioning

confidence: 90%

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A variable immunoreceptor in a subpopulation of human neutrophils

Püellmann

Kaminski²,

Vogel³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Neutrophils are thought to rely solely on nonspecific immune mechanisms. Here we provide molecular biological, immunological, ultrastructural, and functional evidence for the presence of a T cell receptor (TCR)-based variable immunoreceptor in a 5-8% subpopulation of human neutrophils. We demonstrate that these peripheral blood neutrophils express variable and individualspecific TCR␣␤ repertoires and the RAG1͞RAG2 recombinase complex. The proinflammatory cytokine granulocyte colonystimulating factor regulates expression of the neutrophil immunoreceptor and RAG1͞RAG2 in vivo. Specific engagement of the neutrophil TCR complex protects from apoptosis and stimulates secretion of the neutrophil-activating chemokine IL-8. Our results, which also demonstrate the presence of the TCR in murine neutrophils, suggest the coexistence of a variable and an innate host defense system in mammalian neutrophils.innate immune system ͉ neutrophil granulocyte ͉ T cell receptor

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Section: Resultsmentioning

confidence: 90%

“…TCR V␣ and V␤ mRNA expression profiling and size spectratyping of the antigen-binding V␣ and V␤ CDR3 regions were performed as previously reported (11,12). CDR3 spectratypes were assessed on an ABI 310 Genetic Analyzer capillary sequencer (Applied Biosystems, Toroed, Norway).…”

Section: Immunocytochemistry Flow Cytometry and Immunogold Electronmentioning

confidence: 99%

A variable immunoreceptor in a subpopulation of human neutrophils

Püellmann

Kaminski²,

Vogel³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Analyses of the pseudogenes BV10 and BV19 were excluded from this study. 12 A measure of 1 ml of each amplified products was mixed with 2.0 l 100% formamide, heated at 901C for 3 min and electrophoresed on a 6.75% denaturing polyacrylamide gel. The distribution of CDR3 size within the amplified product of each BV subfamily was analyzed with an automatic sequencer (Applied Biosystems Division, Foster City, CA, USA) equipped with a computer program allowing the determination of the fluorescence intensity of each band.…”

Section: Spectratyping Of Complementarity-determining Region 3 (Cdr3)mentioning

confidence: 99%

Expansion and activation of minor histocompatibility antigen HY-specific T cells associated with graft-versus-leukemia response

Takami

Sugimori

Feng

et al. 2004

Bone Marrow Transplant

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Summary:The immune system of females is capable of recognizing and reacting against the male-specific minor histocompatibility antigen (mHA), HY. Thus, cytotoxic T-lymphocytes (CTLs) recognizing this antigen may be useful in eradicating leukemic cells of a male patient if they can be generated in vivo or in vitro from a human leukocyte antigen (HLA)-identical female donor. The HLA-A*0201-restricted HY antigen, FIDSYICQV, is a malespecific mHA. Using HLA-A2/HY peptide tetrameric complexes, we reveal a close association between the emergence of HY peptide-specific CD8 þ T cells in peripheral blood and molecular remission of relapsed BCR/ABL þ chronic myelogenous leukemia in lymphoid blast crisis in a patient who underwent female-to-male transplantation. Assessment of intracellular cytokine levels identified T cells that produce interferon-c in response to the HY peptide during the presence of HY tetramer-positive T cells. These results indicate that transplant with allogeneic HY-specific CTLs has therapeutic potential for relapsed leukemia, and that expansion of such T cells may be involved in the development of a graft-versus-leukemia response against lymphoblastic leukemia cells.

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“…The T cell receptor (TCR) Vb repertoire of CTL was examined by flow cytometry. 18 In brief, 10-14 days after every stimulation (immediately prior to the next stimulation), 5 24 In some cases, T cells bearing distinctive TCR Vb's were positively selected with anti-PE microbeads (Miltenyi Biotec. Inc., Auburn, CA, USA) according to the manufacturer's instruction in further experiments.…”

Section: Patients and Respondersmentioning

confidence: 99%

Tissue-restricted T cell alloresponses across HLA barriers: selection and identification of leukemia-restricted CTL in HLA-mismatched stimulator–responder pairs

Fujiwara

Sconocchia

Melenhorst

et al. 2003

Bone Marrow Transplant

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Summary:Exploiting the graft-versus-leukemia (GVL) effect in mismatched transplants requires its separation from graftversus-host disease (GVHD). We generated leukemiaspecific cytotoxic T lymphocytes (CTL) in three haplotype-mismatched, two class I-mismatched and two single HLA-A locus-matched stimulator-responder pairs. Six patients with chronic myelogenous leukemia and one patient with acute myeloid leukemia transformed from MDS were studied. CTL generated after 10 days stimulation with unselected leukemic peripheral blood mononuclear cells inhibited leukemic CFU-GM colony growth (485% at 10:1 effector:target ratio) with no third-party colony inhibition. In five pairs, responders were cultured separately with leukemia cells, PHA-B or LCL from the stimulator. After 2-4 restimulations, the T cell repertoire was examined by flow analysis using Vb-specific antibodies. Test cultures (but not controls) showed preferential expansion of 1-4 Vb families either common to two or more stimulators or unique to a particular stimulator. Notably, we elicited leukemia-specific TCR Vb expansions on four out of five occasions. In two pairs, responder cells selected for the appropriate leukemia-specific Vb family were shown to have leukemia-specific cytotoxicity. These leukemia-restricted T-cells were CD8+ or CD4+ and CD25+ or CD57+. The results support the development of strategies to selectively deplete GVHD and conserve GVL reactivity in mismatched transplants. Bone Marrow Transplantation (2003) 32, 371-378. doi:10.1038/sj.bmt.1704142Keywords: leukemia-restriction; cytotoxic T-lymphocytes; HLA-mismatched; stem cell transplant The curative effect of allogeneic bone marrow transplantation (allo-BMT) from an HLA-identical donor is well established for a variety of hematological malignancies. Nevertheless, despite the increasing availability of unrelated donors, a suitable HLA-identical donor cannot be identified in a timely fashion for at least 50% of patients. 2,3Animal transplantation models indicate that powerful antitumor cytotoxic T lymphocyte (CTL) can be elicited in an MHC-mismatched setting.4,5 These observations support limited clinical experience in HLA-mismatched transplants indicating a strong graft-versus-leukemia (GVL) effect in high-risk patients with advanced leukemia and in leukemia relapsing after BMT treated with donor lymphocyte infusions.6-9 However, it is also clear that HLA disparity increases the risk of severe graft-versus-host disease (GVHD).10-12 As a result of the risk from GVHD, current HLA-mismatched transplant protocols use T cell depletion and potent immunosuppression to prevent GVHD, which in turn compromises the GVL effect. Separation of GVL alloresponses from the GVHD T cell alloresponse would permit the full exploitation of the therapeutic effect of the haplotype-mismatched transplant. Previous studies in HLA-matched transplants have defined an immunological basis for separating T cell clones with GVHD or GVL alloresponsiveness; while many alloantigens are shared between hematopoietic and nonhe...

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Mitogens, superantigens, and nominal antigens elicit distinctive patterns of TCRB CDR3 diversity

Cited by 65 publications

References 26 publications

A variable immunoreceptor in a subpopulation of human neutrophils

A variable immunoreceptor in a subpopulation of human neutrophils

Expansion and activation of minor histocompatibility antigen HY-specific T cells associated with graft-versus-leukemia response

Tissue-restricted T cell alloresponses across HLA barriers: selection and identification of leukemia-restricted CTL in HLA-mismatched stimulator–responder pairs

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