共查询到20条相似文献,搜索用时 31 毫秒
1.
Alves PM Faure O Graff-Dubois S Cornet S Bolonakis I Gross DA Miconnet I Chouaib S Fizazi K Soria JC Lemonnier FA Kosmatopoulos K 《Cancer immunology, immunotherapy : CII》2006,55(12):1515-1523
STEAP is a recently identified protein shown to be particularly overexpressed in prostate cancer and also present in numerous human cancer cell lines from prostate, pancreas, colon, breast, testicular, cervical, bladder and ovarian carcinoma, acute lymphocytic leukemia and Ewing sarcoma. This expression profile renders STEAP an appealing candidate for broad cancer immunotherapy. In order to investigate if STEAP is a tumor antigen that can be targeted by specific CD8+ T cells, we identified two high affinity HLA-A*0201 restricted peptides (STEAP86–94 and STEAP262–270). These peptides were immunogenic in vivo in HLA-A*0201 transgenic HHD mice. Peptide specific murine CD8 T cells recognized COS-7 cells co-transfected with HHD (HLA-A*0201) and STEAP cDNA constructs and also HLA-A*0201+ STEAP+ human tumor cells. Furthermore, STEAP86–94 and STEAP262–270 stimulated specific CD8+ T cells from HLA-A*0201+ healthy donors, and these peptide specific CD8+ T cells recognized STEAP positive human tumor cells in an HLA-A*0201-restricted manner. Importantly, STEAP86–94-specific T cells were detected and reactive in the peripheral blood mononuclear cells in NSCLC and prostate cancer patients ex vivo. These results show that STEAP can be a target of anti-tumor CD8+ T cells and that STEAP peptides can be used for a broad-spectrum-tumor immunotherapy. 相似文献
2.
Jennifer R. Habel Andrea T. Nguyen Louise C. Rowntree Christopher Szeto Nicole A. Mifsud E. Bridie Clemens Liyen Loh Weisan Chen Steve Rockman Jane Nelson Jane Davies Adrian Miller Steven Y. C. Tong Jamie Rossjohn Stephanie Gras Anthony W. Purcell Luca Hensen Katherine Kedzierska Patricia T. Illing 《PLoS pathogens》2022,18(3)
HLA-A*11:01 is one of the most prevalent human leukocyte antigens (HLAs), especially in East Asian and Oceanian populations. It is also highly expressed in Indigenous people who are at high risk of severe influenza disease. As CD8+ T cells can provide broadly cross-reactive immunity to distinct influenza strains and subtypes, including influenza A, B and C viruses, understanding CD8+ T cell immunity to influenza viruses across prominent HLA types is needed to rationally design a universal influenza vaccine and generate protective immunity especially for high-risk populations. As only a handful of HLA-A*11:01-restricted CD8+ T cell epitopes have been described for influenza A viruses (IAVs) and epitopes for influenza B viruses (IBVs) were still unknown, we embarked on an epitope discovery study to define a CD8+ T cell landscape for HLA-A*11:01-expressing Indigenous and non-Indigenous Australian people. Using mass-spectrometry, we identified IAV- and IBV-derived peptides presented by HLA-A*11:01 during infection. 79 IAV and 57 IBV peptides were subsequently screened for immunogenicity in vitro with peripheral blood mononuclear cells from HLA-A*11:01-expressing Indigenous and non-Indigenous Australian donors. CD8+ T cell immunogenicity screening revealed two immunogenic IAV epitopes (A11/PB2320-331 and A11/PB2323-331) and the first HLA-A*11:01-restricted IBV epitopes (A11/M41-49, A11/NS1186-195 and A11/NP511-520). The immunogenic IAV- and IBV-derived peptides were >90% conserved among their respective influenza viruses. Identification of novel immunogenic HLA-A*11:01-restricted CD8+ T cell epitopes has implications for understanding how CD8+ T cell immunity is generated towards IAVs and IBVs. These findings can inform the development of rationally designed, broadly cross-reactive influenza vaccines to ensure protection from severe influenza disease in HLA-A*11:01-expressing individuals. 相似文献
3.
Here, we sought to determine whether peptide vaccines designed harbor both class I as well as class II restricted antigenic motifs could concurrently induce CD4 and CD8 T cell activation against autologous tumor antigens. Based on our prior genome-wide interrogation of human prostate cancer tissues to identify genes over-expressed in cancer and absent in the periphery, we targeted SIM2 as a prototype autologous tumor antigen for these studies. Using humanized transgenic mice we found that the 9aa HLA-A*0201 epitope, SIM2237–245, was effective at inducing an antigen specific response against SIM2-expressing prostate cancer cell line, PC3. Immunization with a multi-epitope peptide harboring both MHC-I and MHC-II restricted epitopes induced an IFN-γ response in CD8 T cells to the HLA-A*0201-restricted SIM2237–245 epitope, and an IL-2 response by CD4 T cells to the SIM2240–254 epitope. This peptide was also effective at inducing CD8+ T-cells that responded specifically to SIM2-expressing tumor cells. Collectively, the data presented in this study suggest that a single peptide containing multiple SIM2 epitopes can be used to induce both a CD4 and CD8 T cell response, providing a peptide-based vaccine formulation for potential use in immunotherapy of various cancers. 相似文献
4.
Mathilde Bobinet Virginie Vignard Anne Rogel Amir Khammari Brigitte Dreno Francois Lang Nathalie Labarriere 《PloS one》2012,7(12)
MELOE-1 is an overexpressed melanoma antigen containing a HLA-A2 restricted epitope, involved in melanoma immunosurveillance of patients adoptively transferred with tumour infiltrating lymphocytes (TIL). The use of the full-length antigen (46 aa) for anti-melanoma vaccination could be considered, subject to the presence of Th epitopes all along MELOE-1 sequence. Thus, in this study we evaluated in vitro the immunoprevalence of the different regions of MELOE-1 (i.e. their ability to induce CD4 T cell responses in vitro from PBMC). Stimulation of PBMC from healthy subjects with MELOE-1 induced the amplification of CD4 T cells specific for various regions of the protein in multiple HLA contexts, for each tested donor. We confirmed these results in a panel of melanoma patients, and documented that MELOE-1 specific CD4 T cells, were mainly Th1 cells, presumably favourable to the amplification of CD8 specific T cells. Using autologous DC, we further showed that these class II epitopes could be naturally processed from MELOE-1 whole protein and identified minimal epitopes derived from each region of MELOE-1, and presented in four distinct HLA contexts. In conclusion, vaccination with MELOE-1 whole polypeptide should induce specific Th1 CD4 responses in a majority of melanoma patients, stimulating the amplification of CD8 effector cells, reactive against melanoma cells. 相似文献
5.
Wilkinson R Woods K D'Rozario R Prue R Vari F Hardy MY Dong Y Clements JA Hart DN Radford KJ 《Cancer immunology, immunotherapy : CII》2012,61(2):169-179
Immunotherapy is a promising new treatment for patients with advanced prostate and ovarian cancer, but its application is
limited by the lack of suitable target antigens that are recognized by CD8+ cytotoxic T lymphocytes (CTL). Human kallikrein 4 (KLK4) is a member of the kallikrein family of serine proteases that is significantly overexpressed in malignant versus healthy
prostate and ovarian tissue, making it an attractive target for immunotherapy. We identified a naturally processed, HLA-A*0201-restricted
peptide epitope within the signal sequence region of KLK4 that induced CTL responses in vitro in most healthy donors and prostate cancer patients tested. These CTL lysed HLA-A*0201+
KLK4
+ cell lines and KLK4 mRNA-transfected monocyte-derived dendritic cells. CTL specific for the HLA-A*0201-restricted KLK4 peptide were more readily expanded to a higher frequency in vitro compared to the known HLA-A*0201-restricted epitopes from
prostate cancer antigens; prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase
(PAP). These data demonstrate that KLK4 is an immunogenic molecule capable of inducing CTL responses and identify it as an attractive target for prostate and ovarian
cancer immunotherapy. 相似文献
6.
Iero M Squarcina P Romero P Guillaume P Scarselli E Cerino R Carrabba M Toutirais O Parmiani G Rivoltini L 《Cancer immunology, immunotherapy : CII》2007,56(12):1979-1991
The use of “altered peptide ligands” (APL), epitopes designed for exerting increased immunogenicity as compared with native
determinants, represents nowadays one of the most utilized strategies for overcoming immune tolerance to self-antigens and
boosting anti-tumor T cell-mediated immune responses. However, the actual ability of APL-primed T cells to cross-recognize
natural epitopes expressed by tumor cells remains a crucial concern. In the present study, we show that CAP1-6D, a superagonist
analogue of a carcinoembriyonic antigen (CEA)-derived HLA-A*0201-restricted epitope widely used in clinical setting, reproducibly
promotes the generation of low-affinity CD8+ T cells lacking the ability to recognized CEA-expressing colorectal carcinoma (CRC) cells. Short-term T cell cultures, obtained
by priming peripheral blood mononuclear cells from HLA-A*0201+ healthy donors or CRC patients with CAP1-6D, were indeed found to heterogeneously cross-react with saturating concentrations
of the native peptide CAP1, but to fail constantly lysing or recognizing through IFN- γ release CEA+CRC cells. Characterization of anti-CAP1-6D T cell avidity, gained through peptide titration, CD8-dependency assay, and staining
with mutated tetramers (D227K/T228A), revealed that anti-CAP1-6D T cells exerted a differential interaction with the two CEA
epitopes, i.e., displaying high affinity/CD8-independency toward the APL and low affinity/CD8-dependency toward the native
CAP1 peptide. Our data demonstrate that the efficient detection of self-antigen expressed by tumors could be a feature of
high avidity CD8-independent T cells, and underline the need for extensive analysis of tumor cross-recognition prior to any
clinical usage of APL as anti-cancer vaccines. 相似文献
7.
An additional ORF on meloe cDNA encodes a new melanoma antigen, MELOE-2, recognized by melanoma-specific T cells in the HLA-A2 context 总被引:1,自引:0,他引:1
Yann Godet Agnès Moreau-Aubry Dimitri Mompelat Virginie Vignard Amir Khammari Brigitte Dreno Francois Lang Francine Jotereau Nathalie Labarriere 《Cancer immunology, immunotherapy : CII》2010,59(3):431-439
8.
Tang Y Lin Z Ni B Wei J Han J Wang H Wu Y 《Cancer immunology, immunotherapy : CII》2007,56(3):319-329
Tyrosinase-related protein-2 (TRP-2) is a non-mutated melanocyte differentiation antigen. The TRP-2-recognizing CD8+ T cells can evoke immune responses to melanoma in both humans and mice. Developing epitopes with amino acid replacements
in their sequences might improve the low immunogenicity against this ‘self’ tumor antigen. We designed altered peptide ligands
(APLs) of TRP-2(180–188) (SVYDFFVWL) with preferred primary and auxiliary HLA-A*0201 molecule anchor residue replacement. These APLs were screened
for MHC-affinity by affinity prediction plots and molecular dynamics simulation, and analyzed in vitro for stability and binding-affinity
to molecular HLA-A*0201. We also investigated the CTLs activities induced by TRP-2 wild-type epitope and the APLs both in
vitro in human PBMCs and HLA-A2.1/Kb transgenic mice. The results indicate that TRP-2 2M analog simultaneously had stronger binding-affinity and a lower dissociation
rate to HLA-A*0201, than wild-type peptide. In addition, the analog 2M was superior to other APLs and wild-type epitope in
terms of immunological efficacy ex vivo as measured by the ELISPOT assays of IFN-γ and granzyme B. These results demonstrate
that TRP-2 2M is an agonist epitope that can induce anti-tumor immunity superior to its wild-type epitope, and has potential
application in peptide-mediated immunotherapy. 相似文献
9.
《Peptides》2016
The TcTLE peptide (TLEEFSAKL) is a CD8+ T cell HLA-A*0201-restricted epitope derived from the Trypanosoma cruzi KMP-11 protein that is efficiently processed, presented and recognized by CD8+ T cells from chagasic patients. Since the immunogenic properties of wild-type epitopes may be enhanced by suitable substitutions in secondary anchor residues, we have studied the effect of introducing specific mutations at position 3, 6 and 7 of the TcTLE peptide. Mutations (E3L, S6V and A7F) were chosen on the basis of in silico predictions and in vitro assays were performed to determine the TcTLE-modified peptide binding capacity to the HLA-A*0201 molecule. In addition, the functional activity of peptide-specific CD8+ T cells in HLA-A2+ chagasic patients was also interrogated. In contrast to bioinformatics predictions, the TcTLE-modified peptide was found to have lower binding affinity and stability than the original peptide. Nevertheless, CD8+ T cells from chronic chagasic patients recognized the TcTLE-modified peptide producing TNF-α and INF-γ and expressing CD107a/b, though in less extension than the response triggered by the original peptide. Overall, although the amino acids at positions 3, 6 and 7 of TcTLE are critical for the peptide affinity, they have a limited effect on the immunogenic properties of the TcTLE epitope. 相似文献
10.
Eftychia Lekka Angelos D. Gritzapis Sonia A. Perez Nikolaos Tsavaris Ioannis Missitzis Avgi Mamalaki Michael Papamichail Constantin N. Baxevanis 《Cancer immunology, immunotherapy : CII》2010,59(5):715-727
Our aim is to develop peptide vaccines that stimulate tumor antigen-specific T-lymphocyte responses against frequently detected
cancers. We describe herein a novel HLA-A*0201-restricted epitope, encompassing amino acids 828–836 (residues QIAKGMSYL),
which is naturally presented by various HER-2/neu
+ tumor cell lines. HER-2/neu(828-836), [HER-2(9828)], possesses two anchor residues and stabilized HLA-A*0201 on T2 cells in a concentration-dependent Class I binding assay.
This peptide was stable for 3.5 h in an off-kinetic assay. HER-2(9828) was found to be immunogenic in HLA-A*0201 transgenic (HHD) mice inducing peptide-specific and functionally potent CTL and
long-lasting anti-tumor immunity. Most important, using HLA-A*0201 pentamer analysis we could detect increased ex vivo frequencies
of CD8+ T-lymphocytes specifically recognizing HER-2(9828) in 8 out of 20 HLA-A*0201+ HER-2/neu
+ breast cancer patients. Moreover, HER-2(9828)-specific human CTL recognized the tumor cell line SKOV3.A2 as well as the primary RS.A2.1.DR1 tumor cell line both expressing
HER-2/neu and HLA-A*0201. Finally, therapeutic vaccination with HER-2(9828) in HHD mice was proven effective against established transplantable ALC.A2.1.HER tumors, inducing complete tumor regression
in 50% of mice. Our data encourage further exploitation of HER-2(9828) as a promising candidate for peptide-based cancer vaccines. 相似文献
11.
Geluk A van Meijgaarden KE Franken KL Drijfhout JW D'Souza S Necker A Huygen K Ottenhoff TH 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(11):6463-6471
CD8(+) T cells are thought to play an important role in protective immunity to tuberculosis. Although several nonprotein ligands have been identified for CD1-restricted CD8(+) CTLs, epitopes for classical MHC class I-restricted CD8(+) T cells, which most likely represent a majority among CD8(+) T cells, have remained ill defined. HLA-A*0201 is one of the most prevalent class I alleles, with a frequency of over 30% in most populations. HLA-A2/K(b) transgenic mice were shown to provide a powerful model for studying induction of HLA-A*0201-restricted immune responses in vivo. The Ag85 complex, a major component of secreted Mycobacterium tuberculosis proteins, induces strong CD4(+) T cell responses in M. tuberculosis-infected individuals, and protection against tuberculosis in Ag85-DNA-immunized animals. In this study, we demonstrate the presence of HLA class I-restricted, CD8(+) T cells against Ag85B of M. tuberculosis in HLA-A2/K(b) transgenic mice and HLA-A*0201(+) humans. Moreover, two immunodominant Ag85 peptide epitopes for HLA-A*0201-restricted, M. tuberculosis-reactive CD8(+) CTLs were identified. These CD8(+) T cells produced IFN-gamma and TNF-alpha and recognized Ag-pulsed or bacillus Calmette-Guérin-infected, HLA-A*0201-positive, but not HLA-A*0201-negative or uninfected human macrophages. This CTL-mediated killing was blocked by anti-CD8 or anti-HLA class I mAb. Using fluorescent peptide/HLA-A*0201 tetramers, Ag85-specific CD8(+) T cells could be visualized in bacillus Calmette-Guérin-responsive, HLA-A*0201(+) individuals. Collectively, our results demonstrate the presence of HLA class I-restricted CD8(+) CTL against a major Ag of M. tuberculosis and identify Ag85B epitopes that are strongly recognized by HLA-A*0201-restricted CD8(+) T cells in humans and mice. These epitopes thus represent potential subunit components for the design of vaccines against tuberculosis. 相似文献
12.
13.
Mingjun Wang Bingnan Yin Satoko Matsueda Lijuan Deng Ying Li Wei Zhao Jia Zou Qingtian Li Christopher Loo Rong-Fu Wang Helen Y. Wang 《PloS one》2013,8(2)
Background
A large number of human tumor-associated antigens that are recognized by CD8+ T cells in a human leukocyte antigen class I (HLA-I)-restricted fashion have been identified. Special AT-rich sequence binding protein 1 (SATB1) is highly expressed in many types of human cancers as part of their neoplastic phenotype, and up-regulation of SATB1 expression is essential for tumor survival and metastasis, thus this protein may serve as a rational target for cancer vaccines.Methodology/Principal Findings
Twelve SATB1-derived peptides were predicted by an immuno-informatics approach based on the HLA-A*02 binding motif. These peptides were examined for their ability to induce peptide-specific T cell responses in peripheral blood mononuclear cells (PBMCs) obtained from HLA-A*02+ healthy donors and/or HLA-A*02+ cancer patients. The recognition of HLA-A*02+ SATB1-expressing cancer cells was also tested. Among the twelve SATB1-derived peptides, SATB1565–574 frequently induced peptide-specific T cell responses in PBMCs from both healthy donors and cancer patients. Importantly, SATB1565–574-specific T cells recognized and killed HLA-A*02+ SATB1+ cancer cells in an HLA-I-restricted manner.Conclusions/Significance
We have identified a novel HLA-A*02-restricted SATB1-derived peptide epitope recognized by CD8+ T cells, which, in turn, recognizes and kills HLA-A*02+ SATB1+ tumor cells. The SATB1-derived epitope identified may be used as a diagnostic marker as well as an immune target for development of cancer vaccines. 相似文献14.
Mars LT Bauer J Gross DA Bucciarelli F Firat H Hudrisier D Lemonnier F Kosmatopoulos K Liblau RS 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(8):5090-5098
Multiple sclerosis (MS) is a demyelinating inflammatory disease of the CNS. Though originally believed to be CD4-mediated, additional immune effector mechanisms, including myelin-specific CD8(+) T cells, are now proposed to participate in the pathophysiology of MS. To study the immunologic and encephalitogenic behavior of HLA-A*0201-binding myelin-derived epitopes in vivo, we used a humanized HLA-A*0201-transgenic mouse model. Eight HLA-A*0201-binding peptides derived from myelin oligodendrocyte glycoprotein (MOG), an immunodominant myelin self-Ag, were identified in silico. After establishing their relative affinity for HLA-A*0201 and their capacity to form stable complexes with HLA-A*0201 in vitro, their immunological characteristics were studied in HLA-A*0201-transgenic mice. Five MOG peptides, which bound stably to HLA-A*0201 exhibited strong immunogenicity by inducing a sizeable MOG-specific HLA-A*0201-restricted CD8(+) T cell response in vivo. Of these five candidate epitopes, four were processed by MOG-transfected RMA target cells and two peptides proved immunodominant in vivo in response to a plasmid-encoding native full-length MOG. One of the immunodominant MOG peptides (MOG(181)) generated a cytotoxic CD8(+) T cell response able to aggravate CD4(+)-mediated EAE. Therefore, this detailed in vivo characterization provides a hierarchy of candidate epitopes for MOG-specific CD8(+) T cell responses in HLA-A*0201 MS patients identifying the encephalitogenic MOG(181) epitope as a primary candidate. 相似文献
15.
Visus C Ito D Dhir R Szczepanski MJ Chang YJ Latimer JJ Grant SG DeLeo AB 《Cancer immunology, immunotherapy : CII》2011,60(7):919-929
Hydroxysteroid (17β) dehydrogenase type 12 (HSD17B12) is a multifunctional isoenzyme functional in the conversion of estrone
to estradiol (E2), and elongation of long-chain fatty acids, in particular the conversion of palmitic to archadonic (AA) acid,
the precursor of sterols and the inflammatory mediator, prostaglandin E2. Its overexpression together with that of COX-2 in breast carcinoma is associated with a poor prognosis. We have identified
the HSD17B12114–122 peptide (IYDKIKTGL) as a naturally presented HLA-A*0201 (HLA-A2)-restricted CD8+ T-cell-defined epitope. The HSD17B12114–122 peptide, however, is poorly immunogenic in its in vitro ability to induce peptide-specific CD8+ T cells. Acting as an “optimized peptide”, a peptide (TYDKIKTGL), which is identical to the HSD17B12114–122 peptide except for threonine at residue 1, was required for inducing in vitro the expansion of CD8+ T-cell effectors cross-reactive against the HSD17B12114–122 peptide. In IFN-γ ELISPOT assays, these effector cells recognize HSD17B12114–122 peptide-pulsed target cells, as well as HLA-A2+ squamous cell carcinoma of the head and neck (SCCHN) and breast carcinoma cell lines overexpressing HSD17B12 and naturally
presenting the epitope. Whereas growth inhibition of a breast carcinoma cell line induced by HSD17B12 knockdown was only reversed
by AA, in a similar manner, the growth inhibition of the SCCHN PCI-13 cell line by HSD17B12 knockdown was reversed by E2 and
AA. Our findings provide the basis for future studies aimed at developing cancer vaccines for targeting HSD17B12, which apparently
can be functional in critical metabolic pathways involved in inflammation and cancer. 相似文献
16.
Slingluff CL Colella TA Thompson L Graham DD Skipper JC Caldwell J Brinckerhoff L Kittlesen DJ Deacon DH Oei C Harthun NL Huczko EL Hunt DF Darrow TL Engelhard VH 《Cancer immunology, immunotherapy : CII》2000,48(12):661-672
Melanoma-reactive HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) lines generated in vitro lyse autologous and HLA-matched
allogeneic melanoma cells and recognize multiple shared peptide antigens from tyrosinase, MART-1, and Pmel17/gp100. However,
a subset of melanomas fail to be lysed by these T cells. In the present report, four different HLA-A*0201+ melanoma cell lines not lysed by melanoma-reactive allogeneic CTL have been evaluated in detail. All four are deficient in
expression of the melanocytic differentiation proteins (MDP) tyrosinase, Pmel17/gp100, gp75/trp-1, and MART-1/Melan-A. This
concordant loss of multiple MDP explains their resistance to lysis by melanoma-reactive allogeneic CTL and confirms that a
subset of melanomas may be resistant to tumor vaccines directed against multiple MDP-derived epitopes. All four melanoma lines
expressed normal levels of HLA-A*0201, and all were susceptible to lysis by xenoreactive-peptide-dependent HLA-A*0201-specific
CTL clones, indicating that none had identifiable defects in antigen-processing pathways. Despite the lack of shared MDP-derived
antigens, one of these MDP-negative melanomas, DM331, stimulated an effective autologous CTL response in vitro, which was
restricted to autologous tumor reactivity. MHC-associated peptides isolated by immunoaffinity chromatography from HLA-A1 and
HLA-A2 molecules of DM331 tumor cells included at least three peptide epitopes recognized by DM331 CTL and restricted by HLA-A1
or by HLA-A*0201. Recognition of these CTL epitopes cannot be explained by defined, shared melanoma antigens; instead, unique
or undefined antigens must be responsible for the autologous-cell-specific anti-melanoma response. These findings suggest
that immunotherapy directed against shared melanoma antigens should be supplemented with immunotherapy directed against unique
antigens or other undefined antigens, especially in patients whose tumors do not express MDP.
Received: 31 October 1997 / Accepted: 4 August 1999 相似文献
17.
Leptospirosis is an important zoonosis in humans. Immunity against leptospiral infection was thought to be primarily humoral, and limited studies have addressed the role of CD8+ T cells. Leptospiral immunoglobulin-like protein A (LigA) is an important protective antigen of Leptospira and a potential target for Leptospira-specific cell-mediated immunity. In this study, twenty LigA-derived peptides were tested their binding affinity and stability for the HLA-A*0201 molecule. Peptides with high binding affinity and stability for HLA-A*0201 were then assessed their capacity to elicit specific cytotoxic T-lymphocyte (CTL) responses using cytotoxicity, ELISPOT assays for IFN-γ and HLA-A*0201-peptide tetramer assays. We identified a HLA-A*0201-restricted epitope, LigA305–313 KLIVTPAAL in Leptospira LigA. CTLs specific for LigA305–313 were elicited both in HLA-A2.1/Kb transgenic mice and in patients with a clinical and/or laboratory diagnosis of leptospirosis. Staining of the HLA-A*0201–LigA305–313 tetramer revealed the presence of LigA305–313-specific CTLs in peripheral blood mononuclear cells (PBMCs) sourced from five patients infected with three different serovars of Leptospira. In conclusion, we report the existence of specific cytotoxic CD8+ T cells in patients with leptospirosis and we suggest that the newly identified epitope, LigA305–313, will be helpful in enhancing the understanding of the mechanism of immunity to leptospirosis. 相似文献
18.
Identification of a new HLA-A*0201-restricted cytotoxic T lymphocyte epitope from CML28 总被引:1,自引:0,他引:1
Han JF Zhao TT Liu HL Lin ZH Wang HM Ruan ZH Zou LY Wu YZ 《Cancer immunology, immunotherapy : CII》2006,55(12):1575-1583
Identification of cytotoxic T lymphocyte (CTL) epitopes from additional tumor antigens is essential for the development of specific immunotherapy of malignant tumors. CML28, a recently discovered cancer-testis (CT) antigen from chronic myelogenous leukemia, is considered to be a promising target of tumor-specific immunotherapy. Because HLA-A*0201 is one of the most common histocompatibility molecule in Chinese, we aim at identifying CML28 peptides presented by HLA-A*0201. A panel of CML28-derived antigenic peptides was predicted using a computer-based program. Four peptides with highest predicted score were synthesized and tested for their binding affinities to HLA-A*0201 molecule. Then these peptides were assessed for their immunogenicity to elicit specific immune responses mediated by CTLs both in vitro, from PBMCs sourced from four healthy HLA-A*0201+ donors, and in vivo, in HLA-A*0201 transgenic mice. One of the tested peptides, CML28(173–181), induced peptide-specific CTLs in vitro as well as in vivo, which could specifically secrete IFN-γ and lyse major histocompatibility complex (MHC)-matched tumor cell lines endogenously expressing CML28 antigen and CML28(173–181) pulsed Jurkat-A2/Kb cells, respectively. These results demonstrate that CML28(173–181) is a naturally processed and presented CTL epitope with HLA-A*0201 motif and has a promising immunogenicity both in vitro and in vivo. As CML28 is expressed in a large variety of histological tumors besides chronic myelogenous leukemia, we propose that the newly identified epitope, CML28(173–181), would be of potential use in peptide-based, cancer-specific immunotherapy against a broad spectrum of tumors. 相似文献
19.
RY Zhao NA Mifsud K Xiao KF Chan S Oveissi HM Jackson N Dimopoulos P Guillaume AJ Knights T Lowen NC Robson SE Russell E Scotet ID Davis E Maraskovsky J Cebon IF Luescher W Chen 《PloS one》2012,7(9):e44707
NY-ESO-1 has been a major target of many immunotherapy trials because it is expressed by various cancers and is highly immunogenic. In this study, we have identified a novel HLA-B*1801-restricted CD8+ T cell epitope, NY-ESO-188–96 (LEFYLAMPF) and compared its direct- and cross-presentation to that of the reported NY-ESO-1157–165 epitope restricted to HLA-A*0201. Although both epitopes were readily cross-presented by DCs exposed to various forms of full-length NY-ESO-1 antigen, remarkably NY-ESO-188–96 is much more efficiently cross-presented from the soluble form, than NY-ESO-1157–165. On the other hand, NY-ESO-1157–165 is efficiently presented by NY-ESO-1-expressing tumor cells and its presentation was not enhanced by IFN-γ treatment, which induced immunoproteasome as demonstrated by Western blots and functionally a decreased presentation of Melan A26–35; whereas NY-ESO-188–96 was very inefficiently presented by the same tumor cell lines, except for one that expressed high level of immunoproteasome. It was only presented when the tumor cells were first IFN-γ treated, followed by infection with recombinant vaccinia virus encoding NY-ESO-1, which dramatically increased NY-ESO-1 expression. These data indicate that the presentation of NY-ESO-188–96 is immunoproteasome dependent. Furthermore, a survey was conducted on multiple samples collected from HLA-B18+ melanoma patients. Surprisingly, all the detectable responses to NY-ESO-188–96 from patients, including those who received NY-ESO-1 ISCOMATRIX™ vaccine were induced spontaneously. Taken together, these results imply that some epitopes can be inefficiently presented by tumor cells although the corresponding CD8+ T cell responses are efficiently primed in vivo by DCs cross-presenting these epitopes. The potential implications for cancer vaccine strategies are further discussed. 相似文献
20.
Ciesielski MJ Kozbor D Castanaro CA Barone TA Fenstermaker RA 《Cancer immunology, immunotherapy : CII》2008,57(12):1827-1835
Survivin is a tumor-associated antigen (TAA) that has significant potential for use as a cancer vaccine target. To identify
survivin epitopes that might serve as targets for CTL-mediated, anti-tumor responses, we evaluated a series of survivin peptides
with predicted binding to mouse H2-Kb and human HLA-A*0201 antigens in peptide-loaded dendritic cell (DC) vaccines. H2-Kb-positive, C57BL/6 mice were vaccinated using syngeneic, peptide-loaded DC2.4 cells. Splenocytes from vaccinated mice were
screened by flow cytometry for binding of dimeric H2-Kb:Ig to peptide-specific CD8+ T cells. Two survivin peptides (SVN57–64 and SVN82–89) generated specific CD8+ T cells. We chose to focus on the SVN57–64 peptide because that region of the molecule is 100% homologous to human survivin. A larger peptide (SVN53–67), containing multiple class I epitopes, and a potential class II ligand, was able to elicit both CD8+ CTL and CD4+ T cell
help. We tested the SVN53–67 15-mer peptide in a therapeutic model using a peptide-loaded DC vaccine in C57BL/6 mice with survivin-expressing GL261 cerebral
gliomas. This vaccine produced significant CTL responses and helper T cell-associated cytokine production, resulting in a
significant prolongation of survival. The SVN53–67 vaccine was significantly more effective than the SVN57–64 core epitope as a cancer vaccine, emphasizing the potential benefit of incorporating multiple class I epitopes and associated
cytokine support within a single peptide. 相似文献