Cytotoxic T lymphocytes from HLA-A2 transgenic mice specific for HLA-A2 expressed on human cells.

Bernhard, Eric J.; Le, Anhquyen; Barbosa, James A.; Lacy, Elizabeth; Engelhard, Víctor H.

doi:10.1084/jem.168.3.1157

Cited by 35 publications

(14 citation statements)

References 18 publications

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“…1 Results from in vitro stimulation of human peripheral blood leukocytes using the pp65 495-503 peptide (Table 1) confirm that it functions to stimulate CTLp (CTL precursors) as a memory response from individuals with prior CMV exposure. 13,39,47 To test whether the peptide could also stimulate de novo CTLp without prior virus exposure, a Tg HLA A2.1 mouse model was evaluated.…”

Section: Resultsmentioning

confidence: 86%

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Preclinical development of an adjuvant-free peptide vaccine with activity against CMV pp65 in HLA transgenic mice

Rosa

Wang

Brewer

et al. 2002

Blood

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IntroductionInvestigators have focused on developing transgenic (Tg) mice containing human leukocyte antigen (HLA) alleles such as A*0201 (A2.1) in the class I system or DR1 in the class II system to address the problem of selection of epitopes that bind to major histocompatibility complex (MHC) molecules in an experimental model system. 1,2 Cellular immune responses to vaccines can then be studied in an easily manipulated vertebrate system with immunologic similarities to humans. We and others have characterized a repertoire of cytotoxic T-lymphocyte (CTL) epitopes specific for the immunodominant protein, cytomegalovirus (CMV)-pp65. 3,4 The choice of using CTL epitopes derived from CMV was based upon the absence of a Food and Drug Administration-approved vaccine modality against this significant opportunistic infection of solid organ and hematopoietic cell transplantation (HCT) recipients or its congenital manifestations. [5][6][7] The utility of using HLArestricted CTL epitopes is derived from the fact that HCT recipients are HLA typed and can be selected to be potential responders to the epitope-based vaccine. Reactivation of CMV and viremia are closely monitored during the first several months after HCT, representing a unique opportunity to investigate the properties of a therapeutic vaccine. [8][9][10] CMV-infected cells express pp65 both early and late after infection, making it an appropriate vaccine target. 11,12 Vaccines incorporating them would provide a strategy to immunize against CMV infection in the clinical setting. Since CMV-pp65 contains an HLA A2.1-specific epitope that is recognized by T cells from humans and from mice of the H-2 b background containing an HLA A2.1 or chimeric (human/mouse) A2.1/K b transgene, it has been chosen as a model class I epitope for these studies. 3,13,14 To circumvent allele specificity for the required T-helper (T H ) epitope, a series of T H sequences that promiscuously bind to either human or murine class II MHC alleles have been evaluated in combination with the CMV-pp65 HLA A*0201-restricted epitope. 13,15 In the last decade, investigators have studied the optimal means of delivering peptides corresponding to either CTL or T H epitopes as experimental vaccines. Peptides have been emulsified in adjuvants, complexed to alum, or suspended in liposomes, to name a few of the delivery strategies. [16][17][18] Successful epitope vaccine strategies against viruses, bacteria, and tumor antigens have been developed in mice using these delivery vehicles. 19,20 In addition, The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 U.S.C. section 1734. modification of the primary structure of peptides by incorporating lipids also has been extensively studied in both experimental animals and in man. 21,22 Lipopeptides (lipidated peptides) specific for hepatitis B (HBV), HIV, and tumor antigens have been studied clinically in phase 1 and...

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Section: Resultsmentioning

confidence: 86%

“…1,2 Cellular immune responses to vaccines can then be studied in an easily manipulated vertebrate system with immunologic similarities to humans. We and others have characterized a repertoire of cytotoxic T-lymphocyte (CTL) epitopes specific for the immunodominant protein, cytomegalovirus (CMV)-pp65.…”

Section: Introductionmentioning

confidence: 99%

Preclinical development of an adjuvant-free peptide vaccine with activity against CMV pp65 in HLA transgenic mice

Rosa

Wang

Brewer

et al. 2002

Blood

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“…To be of value, we used transgenic mice carrying a human class I major histocompatibility complex antigen, HLA-A2, to assay the efficacies of the vaccines. Due to the central role of MHC in the generation of an immune response, transgenic mice carrying human MHC products (HLA-A*0201) could provide an important model system in which to assess the induction of an HLA-associated immune response (3,22). Antigen processing and presentation by murine cells can reveal the same set of HLA-restricted antigenic epitopes recognized by human T cells.…”

Section: Cd25mentioning

confidence: 99%

Oral Vaccination with AttenuatedSalmonella entericaStrains Encoding T-Cell Epitopes from Tumor Antigen NY-ESO-1 Induces Specific Cytotoxic T-Lymphocyte Responses

Meng

Dong

Huang

et al. 2010

Clin Vaccine Immunol

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Bacterial fimbriae can accept foreign peptides and display them on the cell surface. A highly efficient gene replacement method was used to generate peptide vaccines based on Salmonella enterica serovar Typhimurium SL3261. The T-cell epitopes (NY-ESO-1 p157-165 and p157-167) from NY-ESO-1, which is a promising target antigen in patients for the specific immune recognition of cancer, were incorporated into the gene encoding AgfA (the major subunit protein of thin aggregative fimbriae of Salmonella) by replacing an equal length of the DNA segment. To improve cytotoxic T-lymphocyte recognition, both termini of the peptide were flanked by double alanine (AA) residues. Immunofluorescence microscopy with AgfA-specific antiserum verified the expression of chimeric AgfA, which was also proved by a Congo red binding assay. Modulating the immune system to control cancer has been a challenge for cancer immunotherapists for many years. A number of clinical trials have indeed demonstrated that objective tumor regressions can occur in the setting of cancer vaccinations (1,19,31

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“…Furthermore, CTL from mice transgenic for a particular human HLA molecule recognized the same HLA-restricted peptide(s) as did CTL of human origin (40,41). It is therefore likely that species-specific differences in antigen processing by mouse and human cells have little effect (42)(43)(44)(45). This system has not previously been applied to bacterial epitopes.…”

Section: Discussionmentioning

confidence: 99%

Recognition of chlamydial antigen by HLA‐B27‐restricted cytotoxic T cells in HLA‐B*2705 transgenic CBA (H‐2^k) mice

Kuon

Lauster

Böttcher

et al. 1997

Arthritis & Rheumatism

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Objective. The association of reactive arthritis (ReA) with HLA‐B27 and the presence of bacterial antigen in joints with ReA suggest that bacterial peptides might be presented by the HLA‐B27 molecule and thus stimulate CD8 T cells. This study was performed to investigate the B27‐restricted cytotoxic T lymphocyte (CTL) response to Chlamydia trachomatis, using the model of HLA‐B27 transgenic mice. Methods. CBA (H‐2k) mice homozygous for HLA‐B*2705 and human β2‐microglobulin expression were immunized with C trachomatis or with the chlamydial 57‐kd heat‐shock protein (hsp57) coupled to latex beads. Cytotoxicity of lymphocytes from in vivo—primed transgenic mice was tested against C trachomatis—infected targets. Blocking experiments were performed with monoclonal antibodies (MAb) against class I major histocompatibility complex molecules. Results. A Chlamydia‐specific lysis of both B27‐transfected and nontransfected target cells was observed. This response could be inhibited by anti‐B27 and anti‐H2 MAb. CTL from mice immunized with hsp57 were not able to lyse Chlamydia‐infected target cells, and Chlamydia‐specific CTL could not destroy targets loaded with hsp57. Conclusion. These results suggest the existence of at least 2 CTL populations in this mouse model: one recognizing peptide of bacteria‐infected cells restricted by HLA‐B*2705 and the other recognizing peptide of bacteria‐infected cells restricted by the murine H‐2Kk molecule. It does not appear that hsp57 is a major target for the CD8 T cell response directed against Chlamydia. This animal model opens the way for identifying bacterial epitopes presented by HLA‐B27, and might thus help to clarify the pathogenesis of B27‐associated diseases.

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Cytotoxic T lymphocytes from HLA-A2 transgenic mice specific for HLA-A2 expressed on human cells.

Cited by 35 publications

References 18 publications

Preclinical development of an adjuvant-free peptide vaccine with activity against CMV pp65 in HLA transgenic mice

Preclinical development of an adjuvant-free peptide vaccine with activity against CMV pp65 in HLA transgenic mice

Oral Vaccination with AttenuatedSalmonella entericaStrains Encoding T-Cell Epitopes from Tumor Antigen NY-ESO-1 Induces Specific Cytotoxic T-Lymphocyte Responses

Recognition of chlamydial antigen by HLA‐B27‐restricted cytotoxic T cells in HLA‐B*2705 transgenic CBA (H‐2^k) mice

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Cytotoxic T lymphocytes from HLA-A2 transgenic mice specific for HLA-A2 expressed on human cells.

Cited by 35 publications

References 18 publications

Preclinical development of an adjuvant-free peptide vaccine with activity against CMV pp65 in HLA transgenic mice

Preclinical development of an adjuvant-free peptide vaccine with activity against CMV pp65 in HLA transgenic mice

Oral Vaccination with AttenuatedSalmonella entericaStrains Encoding T-Cell Epitopes from Tumor Antigen NY-ESO-1 Induces Specific Cytotoxic T-Lymphocyte Responses

Recognition of chlamydial antigen by HLA‐B27‐restricted cytotoxic T cells in HLA‐B*2705 transgenic CBA (H‐2k) mice

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Recognition of chlamydial antigen by HLA‐B27‐restricted cytotoxic T cells in HLA‐B*2705 transgenic CBA (H‐2^k) mice