Different <i>in vivo</i> tolerogenicity of MHC class I peptides

Fändrich, F.; Zhu, X.; Schröder, Jörg; Dresske, Bettina; Henne‐Bruns, Doris; Oswald, Hanno; Zavazava, Nicholas

doi:10.1002/jlb.65.1.16

Cited by 20 publications

(9 citation statements)

References 47 publications

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“…12,13,28 On this basis, several HLA-B7-derived peptides covering residues 56 to 120 were synthesized using the FMOC technique, as we previously described in more detail. 29 Peptides synthesized and used in these experiments are shown on the sequence alignment in Figure 1 and Table 1.…”

Section: Synthesis and Fitc Conjugation Of Mhc-derived Allopeptidesmentioning

confidence: 99%

“…[9][10][11] In other studies, class I-and class II-derived allopeptides were used to induce tolerance. [12][13][14] By studying a series of rat-derived synthetic allo-MHC peptides, immunodominant regions of allogeneic MHC molecules that modulate graft survival were identified. 13 These studies revealed that some regions of MHC class I molecules are not immunogenic and do not modulate alloresponses.…”

Section: Introductionmentioning

confidence: 99%

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HLA-B7 β-pleated sheet-derived synthetic peptides are immunodominant T-cell epitopes regulating alloresponses

Freese

Zavazava

2002

Blood

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Chronic rejection of transplanted allografts is the major cause of graft loss after clinical solid organ transplantation. Recent data link the indirect presentation of allopeptides to chronic graft loss; thus, identification of immunodominant epitopes on major histocompatibility complex (MHC) antigens could significantly contribute to establishing novel ways for monitoring and managing chronic rejection. Here, we show that synthetic allo-MHC-derived peptides covering the polymorphic region 56 to120 of HLA-B7 modulate alloresponses. In particular, the 2 ␤-pleated sheet-derived peptides covering residues 91 to 105 and 96 to 120, respectively, but not sequences from the ␣1 helix, were presented by autologous peripheral blood lymphocytes to induce T-cell proliferation. In addition, the 2 ␤-pleated sheetderived peptides and the ␣1-derived peptide residues 60 to 75 abrogated lysis of HLA-B7 target cells by anti-HLA-B7 cytotoxic T lymphocytes (CTLs). Although most residues between 91 and 120 are normally not directly accessible to T cells, our results indicate that peptides derived from the lower surface of the peptidebinding groove of HLA-B7 are immunodominant in HLA-B7 alloresponses. To characterize the binding and stability of allopeptides to T cells, the 62-70 peptidederived from the 60-75 allopeptide that blocked cytotoxicity of anti-HLA-B7 CTL-was synthesized and coupled with fluorescein isothiocyanate. The peptide specifically labeled anti-B7 CTL, but not anti-HLA-A2 CTL as measured by flow cytometry. Peptide binding to CTL was specific at 4°C and remained stable for 12 hours, whereas it remained stable for less than 2 hours at 37°C. These studies allow the identification of HLA-B7 T-cell epitopes and reveal for the first time a novel, previously unrecognized application of synthetic HLA-derived allopeptides to visualize alloreactive T cells. IntroductionStructural studies show that T-cell receptor (TCR) contacts bind peptide and large stretches of ␣1 and ␣2 major histocompatibility complex (MHC) helices. 1,2 In general, endogenous peptides derived from allo-MHC are seen by T cells as foreign-eliciting alloresponses. 3 T cells may recognize peptide-induced conformational changes, and they may also recognize surface MHC structures in addition to or independent of bound peptide. 4 Furthermore, allospecific cytotoxic T lymphocytes (CTLs) that are peptidedependent and peptide-specific have been described in the literature. 5 In general, however, when donor and recipient MHCs are structurally similar, the endogenous peptide appears to be the dominant target of alloreactive T cells, 5-7 a phenomenon backed by clinical data in graft-versus-host disease. 8 Synthetic allopeptides have been used in many different models to modulate alloresponses and to study alloreactivity. [9][10][11] In other studies, class I-and class II-derived allopeptides were used to induce tolerance. 12-14 By studying a series of rat-derived synthetic allo-MHC peptides, immunodominant regions of allogeneic MHC molecules that modulate graft surviv...

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Section: Synthesis and Fitc Conjugation Of Mhc-derived Allopeptidesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HLA-B7 β-pleated sheet-derived synthetic peptides are immunodominant T-cell epitopes regulating alloresponses

Freese

Zavazava

2002

Blood

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“…Previous approaches towards manipulation of T-cell differentiation have used intrathymic injection of antigens, as proteins [Fandrich et al, 1999;Ilan et al, 1996;Oluwole et al, 1999], cells [Behara et al, 1992] or adenoviruses [DeMatteo et al, 1995;Ilan et al, 1996], leading to transient expression of the foreign protein and reduction of antigen-specific immune responses. The concept of targeting thymus to minimize immune responses have been proposed for many years, however the clinical experience is still lacking.…”

Section: Induction Of Central Tolerancementioning

confidence: 99%

Recent Advances in Immune Modulation

Miao¹

2007

CGT

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Successful gene therapy protocols rely on the hypo-responsiveness of the immune system to transgene products generated from gene transfer vectors. In order to prevent cytotoxic lymphocyte or antibody formation induced by transgene expression, various strategies derived from recent advances in immune tolerance induction protocols have been tested in gene therapy model systems. Current immunosuppressive drugs were used to nonspecifically target T-cell activation, clonal expansion, and differentiation into effector cells. Central tolerance can be induced from intrathymic deletion of T cells with thymically expressed antigens or generation of hematopoietic mixed chimerism. Peripheral tolerance to transgenes may be achieved by several different pathways including deletion of activated/effector T cells by depleting antibodies, generation of T cell apoptosis or anergy by costimulation blockade, and active suppression by T regulatory cells. This review outlines the development of these strategies using various immune modulation regimens and protocols to induce long-term immune tolerance specific to the transgene product.

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“…The spleen and mesenteric lymph nodes were removed aseptically, transferred to sterile phospho-buffered saline (PBS) at 4 o C and pressed through a nylon cell strainer to produce a single cell suspension. Lymphocytes were isolated by Ficoll 400/ Uropolinum 75% density -gradient in centrifugation for 15 min at 4 o C [12].…”

Section: Isolation Of Lymphocytesmentioning

confidence: 99%

Experimental immunology The influence of immunosuppression on apoptosis and necrosis during experimental trichinellosis in mice

Piekarska¹,

Gorczykowski²,

Szczypka³

et al. 2012

cejoi

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A study was carried out to determine the influence of immunosuppressive drug on apoptosis and necrosis lymphocytes in the spleen and mesenteric lymph nodes of mice experimentally infected with Trichinella spiralis. CFW mice were infected with 200 larvae of Trichinella spiralis. Dexametasone was injected intra-peritoneally, at a dose of 25 mg/kg body weight, ten times at 24 hour intervals (between 1-5 and 18-22 day of infection). The lymphocytes obtained from the spleen and mesenteric lymph nodes on 7, 14, 21, 28, 35, 42 and 60 day after infection were incubated using Annexin-V-Fluos Staining Kit. Results of the study demonstrated that dexametasone increased the percentage of apoptotic lymphocytes in the spleen and mesenteric lymph nodes from 14 day after infection in mice infected with T. spiralis and decreased the percentage of the necrotic lymphocytes in both examined lymphatic organs.

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Different in vivo tolerogenicity of MHC class I peptides

Cited by 20 publications

References 47 publications

HLA-B7 β-pleated sheet-derived synthetic peptides are immunodominant T-cell epitopes regulating alloresponses

HLA-B7 β-pleated sheet-derived synthetic peptides are immunodominant T-cell epitopes regulating alloresponses

Recent Advances in Immune Modulation

Experimental immunology The influence of immunosuppression on apoptosis and necrosis during experimental trichinellosis in mice

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