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Role of T-cell receptor V beta 8.3 peptide vaccine in the prevention of experimental autoimmune uveoretinitis

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Chinese Medical Journal 2006年第9期119卷 740-748页

作者： ZHANG Rui YANG Pei-zeng WU Chang-you JIN Hao-li LI Bing HUANG Xiang-kun ZHOU Hong-yan GAO Yang ZHU Lian-xiang Aize Kijlstra Zhongshan Ophthalmic Centre Sun Yat-sen University Guangzhou 510060 China Department of Immunology Sun Yat-sen University Guangzhou 510089 China Division of Immunology Children＇s Hospital Boston Harvard Medical School Boston MA 02115 USA Animal Sciences Group Wageningen University and Research Centre Lelystad Eye Research Institute Maastricht and Department of Ophthalmology Academic Medical Centre University of Amsterdam the Netherlands

Background T-cell receptor （tCR） plays an important role in the development of autoimmune diseases. Recently, it was reported that immunization of animals with tCR peptide derived from the pathogenic cells could prevent autoimmune diseases. the aim of this study was to investigate whether vaccination with a synthetic peptide from the hypervariable region of tCR Vβ 8.3, an experimental autoimmune uveoretinitis （EAU）-associated gene, was able to prevent the disease. Methods EAU was induced in Lewis rats by immunization with IRBP R16 peptide emulsified in complete Freund＇s adjuvant （CFA）. the clinical and histological appearances were scored. Delayed type hypersensitivity （DtH） and lymphocyte proliferation were detected. Cytokine levels of aqueous humour, supernatants of cells from spleen and draining lymph nodes were measured by enzyme linked immunosorbent assay （ELISA）. Gene expression of tCR Vβ8.3 on CD4^＋ t cells was examined by real time quantitative polymerase chain reaction （PCR）. Results After vaccination, the intraocular inflammation was significantly mitigated, antigen specific DtH and lymphocyte proliferation responses were suppressed, interleukin （IL）-2 in aqueous humour, interferon （IFN）-γ and IL-2 produced by the spleen and draining lymph node cells were significantly decreased, whereas the production of IL-4 and IL-10 were increased. the response of draining lymph node cells to tCR Vβ 8.3 peptide was enhanced after vaccination. Inoculation with CFA alone did not affect the severity of EAU and the above parameters. the suppression of EAU was much stronger in the group of four fold inoculations than the group of two fold inoculations. the expression of tCR Vβ 8.3 gene was significantly reduced in the group of fourfold inoculations. Conclusion Vaccination with the synthetic tCR Vβ 8.3 peptide could remarkably inhibit the development of EAU.

关键词： uveoretinitis autoimmune T-cell receptor peptide vaccine

Alterations in thymocyte populations under conditions of endotoxin tolerance

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Chinese Medical Journal 2021年第15期134卷 1855-1865页

作者： Yi-Jing tao Juan-Juan Zhao Li-Hua Rao Song Yang Guo-Liang Zhang Meng-Meng Guo Chao Chen Lin Xu Department of Laboratory Medicine Jiangxi Hospital of Integrated Chinese and Western MedicineNanchangJiangxi 330009China Department of Immunology Zunyi Medical UniversityZunyiGuizhou 563000China

Background:Endotoxin tolerance(Et)is a protective phenomenon in which pre-treatment with a tolerance dose of lipopolysaccharide(LPS)leads to dramatically elevated survival.Accumulating evidence has shown that peripheral t cells contribute to the induction of Et.However,what happens to t cell development in the thymus under Et conditions remains unclear.the purpose of this study was to analyze the alterations in thymocyte populations(double-positive[DP]and single-positive[SP]cells)under Et conditions.Methods:Mice were intraperitoneally injected with LPS at a concentration of 5 mg/kg to establish an LPS tolerance model and were divided into two groups:a group examined 72 h after LPS injection(72-h group)and a group examined 8 days after LPS injection(8-day group).Injection of phosphate-buffered saline was used as a control(control group).Changes in thymus weight,cell counts,and morphology were detected in the three groups.Moreover,surface molecules such as CD4,CD8,CD44,CD69,and CD62L were analyzed using flow cytometry.Furthermore,proliferation,apoptosis,cytokine production,and extracellular signal-regulated kinase(ERK)pathway signaling were analyzed in thymocyte populations.the polymorphism and length of the T-cell receptor(tCR)P chain complementarity-determining region 3(CDR3)were analyzed using capillary electrophoresis DNA laser scanning analysis(ABI 3730).Results:thymus weight and cell counts were decreased in the early stage but recovered by the late stage in a murine model of LPS-induced Et.Moreover,the proportions of DP cells(control:72.130±4.074,72-h:10.600±3.517,8-day:84.770±2.228),CD4+SP cells(control:15.770±4.419,72-h:44.670±3.089,8-day:6.367±0.513),and CD8+SP cells(control:7.000±1.916,72-h:34.030±3.850,8-day:5.133±0.647)were obviously different at different stages of Et.the polymorphism and length of tCR β chain CDR3 also changed obviously,indicating the occurrence of tCR rearrangement and thymocyte diversification.Further analysis showed that the expression of surface molecules,including CD44,CD69,and

关键词： Immune tolerance thymocytes T-cell receptor Gene rearrangement Adaptive immunity

Identification of a CD4 t-cell epitope in the hemagglutinin stalk domain of pandemic H 1N 1 influenza virus and its antigen-driven tCR usage signature in BALB/c mice

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cellular & Molecular Immunology 2017年第6期14卷 511-520页

作者： I-Na Lu Sophie Farinelle Aurelie Sausy Claude P Muller Department of Infection and Immunity Luxembourg Institute of Health Esch-sur-Alzette L-4354 Luxembourg

the stalk region of the influenza virus hemagglutinin is relatively well conserved compared with the globular head domain, which makes it a potential target for use as a universal vaccine against influenza. However, the role of CD4 t cells in the hemagglutinin stalk-specific immune response is not clear. Here we identified a mouse CD4 t-cell epitope that encompasses residues HA2113-131 from the hemagglutinin stalk domain after a sub-lethal infection of influenza. In response to stimulation with the identified epitope, splenocytes derived from the infected mice showed significant polyfunctionality as shown by IL-2, tNF-a and IFN-7 production as well as degranulation. Moreover, mice immunized with the peptide corresponding to this CD4 t-cell epitope exhibited interindividual sharing of the CD4 T-cell receptor I~ sequences, and they had a higher survival rate following a challenge with a lethal dose of pandemic H IN 1 influenza virus. thus, our data demonstrated a crucial role of hemagglutinin stalk-specific CD4 t cells in the host immune resoonse a^ainst influenza virus infection.

关键词： H1N1 hemagglutinin influenza T-cell receptor

CD40 interacts directly with RAG1 and RAG2 in autoaggressive t cells and Fas prevents CD40-induced RAG expression

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cellular & Molecular Immunology 2013年第6期10卷 483-489页

作者： Gisela M Vaitaitis David H Wagner Jr Department of Medicine and Webb-Waring Center University of Colorado Denver Aurora CO USA

CD4＋ t cells expressing CD40 （th40 cells） constitute a pathogenic t-cell subset that is necessary and sufficient to transfer autoimmune disease. We have previously demonstrated that CD40 signals peripheral th40 cells to induce RAG1 and RAG2 expression, proteins necessary for the expression of T-cell receptor （tCR）, leading to tCR revision. the dependency of tCR expression in the thymus on RAG proteins has long been known. However, despite numerous publications, there is controversy as to whether tCR expression can be altered in the periphery, post-thymic selective pressures. therefore, a better understanding of tCR expression in primary peripheral cells is needed. We now show that the CD40 protein itself interacts with RAG1 and RAG2 as well as with Ku70 and translocates to the nucleus in th40 cells. this indicates that the CD40 molecule is closely involved in the mechanism of tCR expression in the periphery. In addition, Fas signals act as a silencing mechanism for CD40-induced RAGs and prevent CD40 translocation to the nucleus. It will be important to further understand the involvement of CD40 in peripheral tCR expression and how tCR revision impacts auto-antigen recognition in order to effectively target and tolerize autoaggressive t cells in autoimmune disease.

关键词： autoimmunity CD40 Fas RAG T-cell receptor

Diversity of yO t-cell antigens

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cellular & Molecular Immunology 2013年第1期10卷 13-20页

作者： Willi K Born M Kemal Aydintug Rebecca L O'Brien Integrated Department of Immunology National Jewish Health Denver CO USA University of Colorado Denver Aurora CO USACorrespondence: Dr WK Born National Jewish Health 1400 Jackson Street GB K409 Denver CO 80206 USA.

In the last two decades, it has become clear that yo t cells recognize a diverse array of antigens including self and foreign, large and small, and peptidic and non-peptidic molecules. In this respect, 78 antigens as a whole resemble more the antigens recognized by antibodies than those recognized by t cells. Because of this antigenic diversity, no single mechanism--such as the major histocompatibility complex （MHC） restriction of ap t cells--is likely to provide a basis for all observed t-cell antigen receptor （tCR）-dependent 78 t-cell responses. Furthermore, available evidence suggests that many individual 78 t cells are poly-specific, probably using different modes of ligand recognition in their responses to unrelated antigens. While posing a unique challenge in the maintenance of self-tolerance, this broad reactivity pattern might enable multiple overlapping uses of 78 t-cell populations, and thus generate a more efficient immune response.

关键词： antigen recognition ligand T-cell receptor yo t cells

Self-activation of Vγ9Vδ2 t cells by exogenous phosphoantigens involves tCR and butyrophilins

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cellular & Molecular Immunology 2021年第8期18卷 1861-1870页

作者： ChloéLaplagne Laetitia Ligat Juliet Foote Frederic Lopez Jean-Jacques Fournié Camille Laurent Salvatore Valitutti Mary Poupot Inserm UMR1037 Centre de Recherches en Cancérologie de ToulouseToulouseFrance Universitétoulouse III Paul-Sabatier ToulouseFrance ERL 5294 CNRS ToulouseFrance IUCt-O ToulouseFrance

the high cytotoxic activity of Vγ9Vδ2 t lymphocytes against tumor cells makes them useful candidates in anticancer therapies.However,the molecular mechanism of their activation by phosphoantigens(PAgs)is not completely known.Many studies have depicted the mechanism of Vγ9Vδ2 t-cell activation by PAg-sensed accessory cells,such as immune presenting cells or tumor cells.In this study,we demonstrated that pure resting Vγ9Vδ2 t lymphocytes can self-activate through exogenous PAgs,involving their tCR and the butyrophilins BtN3A1 and BtN2A1.this is the first time that these three molecules,concurrently expressed at the plasma membrane of Vγ9Vδ2 t cells,have been shown to be involved together on the same and unique t cell during PAg activation.Moreover,the use of probucol to stimulate the inhibition of this self-activation prompted us to propose that ABCA-1 could be implicated in the transfer of exogenous PAgs inside Vγ9Vδ2 t cells before activating them through membrane clusters formed byγ9tCR,BtN3A1 and BtN2A1.the self-activation of Vγ9Vδ2 t cells,which leads to self-killing,can therefore participate in the failure ofγδt cell-based therapies with exogenous PAgs and should be taken into account.

关键词： Vγ9Vδ2 t cells Phosphoantigen Butyrophilins T-cell receptor

Human immune repertoire in hepatitis B virus infection

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World Journal of Gastroenterology 2021年第25期27卷 3790-3801页

作者： Qiao Zhan Jing-Hang Xu Yan-Yan Yu Emily Lo KK Felicianna Hani El-Nezami Zheng Zeng Department of Infectious Diseases Peking University First HospitalBeijing 100034China School of Biological Sciences University of Hong KongHong KongChina Institute of Public Health and Clinical Nutrition School of MedicineUniversity of Eastern FinlandKuopio FI-70211Finland

Hepatitis B virus(HBV)infection is a public health threat that affects 257 million people worldwide and can progress to liver cirrhosis,liver failure,and hepatocellular carcinoma.the HBV antigen-induced adaptive immune response plays an important role in HBV clearance.Immune repertoire sequencing(IRS)has been used to investigate the molecular mechanisms behind the immune system,find novel ways to treat HBV infection,and evaluate the genetic responses and immune characteristics of individuals infected by HBV or immunized by HBV vaccine.this review summarizes the human immune repertoire analysis methodology,and the application of the IRS in the prediction of HBV infection progression,treatment,and vaccination.

关键词： Immune repertoire T-cell receptor B-cell receptor Hepatitis B virus Chronic viral infection High-throughput sequencing

Genetic and environmental factors associated with the diversity and biases of immune system

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Genetic and environmental factors associated with the divers...