scholarly journals Cytotoxic T lymphocyte recognition of the influenza hemagglutinin gene product expressed by DNA-mediated gene transfer.

1984 ◽  
Vol 159 (2) ◽  
pp. 341-354 ◽  
Author(s):  
T J Braciale ◽  
V L Braciale ◽  
T J Henkel ◽  
J Sambrook ◽  
M J Gething
Keyword(s):  
Gene Transfer ◽  
Gene Product ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Type A ◽  
Target Antigen ◽  
Influenza Hemagglutinin ◽  
Ha Gene ◽  
Hemagglutinin Gene ◽  
Target Molecules

We have used the technique of DNA-mediated gene transfer to examine cytotoxic T lymphocyte (CTL) recognition of the product of the cloned A/JAPAN/305/57 hemagglutinin (HA) gene in murine (L929) cells. Using both heterogeneous and homogeneous (clonal) populations of type A influenza-specific CTL, we have demonstrated that the HA molecule can serve as a target antigen for both the subtype-specific and the cross-reactive subpopulations of influenza-specific CTL. Our results also raise the possibility that other virus-specified polypeptides may serve as target molecules for cross-reactive CTL.

HLA class I-restricted lysis of leukemia cells by a CD8+ cytotoxic T-lymphocyte clone specific for WT1 peptide

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 286-293 ◽  
Author(s):  
Hideki Ohminami ◽  
Masaki Yasukawa ◽  
Shigeru Fujita
Keyword(s):  
T Lymphocyte ◽  
Bone Marrow Cells ◽  
Cytotoxic T Lymphocyte ◽  
Wilms Tumor ◽  
Myelogenous Leukemia ◽  
Leukemia Cells ◽  
Target Antigen ◽  
Human Leukemia ◽  
Wt1 Gene ◽  
Normal Cells

Abstract The Wilms tumor (WT1) gene has been reported to be preferentially expressed in acute leukemia cells, regardless of leukemia subtype and chronic myelogenous leukemia cells in blast crisis, but not in normal cells. This finding suggests strongly that WT1 protein is a potential target of immunotherapy for human leukemia. In this study, we established a CD8+ cytotoxic T-lymphocyte (CTL) clone directed against a WT1-derived peptide and examined its immunologic actions on leukemia cells. A CD8+ CTL clone, designated TAK-1, which lysed autologous cells loaded with a WT1-derived 9-mer peptide consisting of the HLA-A24 (HLA-A*2402)-binding motifs was established by stimulating CD8+ T lymphocytes from a healthy individual repeatedly with WT1 peptide-pulsed autologous dendritic cells. TAK-1 was cytotoxic to HLA-A24–positive leukemia cells expressing WT1, but not to HLA-A24–positive lymphoma cells that did not express WT1, HLA-A24–negative leukemia cells, or HLA-A24–positive normal cells. Treating leukemia cells with an antisense oligonucleotide complementary to the WT1 gene resulted in reduced TAK-1-mediated cytotoxicity, suggesting that target antigen of TAK-1 on leukemia cells is the naturally processed WT1 peptide in the context of HLA-A24. TAK-1 did not inhibit colony formation by normal bone marrow cells of HLA-A24–positive individuals. Because WT1 is overexpressed ubiquitously in various types of leukemia cells, but not in normal cells, immunotherapy using WT1 peptide-specific CTL clones should be an efficacious treatment for human leukemia. (Blood. 2000;95:286-293)

HLA class I-restricted lysis of leukemia cells by a CD8+ cytotoxic T-lymphocyte clone specific for WT1 peptide

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 286-293 ◽  
Author(s):  
Hideki Ohminami ◽  
Masaki Yasukawa ◽  
Shigeru Fujita
Keyword(s):  
T Lymphocyte ◽  
Bone Marrow Cells ◽  
Cytotoxic T Lymphocyte ◽  
Wilms Tumor ◽  
Myelogenous Leukemia ◽  
Leukemia Cells ◽  
Target Antigen ◽  
Human Leukemia ◽  
Wt1 Gene ◽  
Normal Cells

The Wilms tumor (WT1) gene has been reported to be preferentially expressed in acute leukemia cells, regardless of leukemia subtype and chronic myelogenous leukemia cells in blast crisis, but not in normal cells. This finding suggests strongly that WT1 protein is a potential target of immunotherapy for human leukemia. In this study, we established a CD8+ cytotoxic T-lymphocyte (CTL) clone directed against a WT1-derived peptide and examined its immunologic actions on leukemia cells. A CD8+ CTL clone, designated TAK-1, which lysed autologous cells loaded with a WT1-derived 9-mer peptide consisting of the HLA-A24 (HLA-A*2402)-binding motifs was established by stimulating CD8+ T lymphocytes from a healthy individual repeatedly with WT1 peptide-pulsed autologous dendritic cells. TAK-1 was cytotoxic to HLA-A24–positive leukemia cells expressing WT1, but not to HLA-A24–positive lymphoma cells that did not express WT1, HLA-A24–negative leukemia cells, or HLA-A24–positive normal cells. Treating leukemia cells with an antisense oligonucleotide complementary to the WT1 gene resulted in reduced TAK-1-mediated cytotoxicity, suggesting that target antigen of TAK-1 on leukemia cells is the naturally processed WT1 peptide in the context of HLA-A24. TAK-1 did not inhibit colony formation by normal bone marrow cells of HLA-A24–positive individuals. Because WT1 is overexpressed ubiquitously in various types of leukemia cells, but not in normal cells, immunotherapy using WT1 peptide-specific CTL clones should be an efficacious treatment for human leukemia. (Blood. 2000;95:286-293)

scholarly journals Oral Vaccination with Attenuated Salmonella enterica Strains Encoding T-Cell Epitopes from Tumor Antigen NY-ESO-1 Induces Specific Cytotoxic T-Lymphocyte Responses

2010 ◽  
Vol 17 (6) ◽  
pp. 889-894 ◽  
Author(s):  
Jia-Zi Meng ◽  
Yu-Jun Dong ◽  
He Huang ◽  
Shuang Li ◽  
Yi Zhong ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Salmonella Enterica ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Response ◽  
Target Antigen ◽  
Immune Recognition ◽  
T Cell Epitopes ◽  
Replacement Method

ABSTRACT 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. Oral immunizations of HLA-A*0201 transgenic mice with recombinant SL3261 strains encoding NY-ESO-1 p157-165 or p157-167 induced NY-ESO-1 p157-165-specific CD8+ T cells, detected by an HLA-A*0201 pentamer, and induced a T-cell response detected by an enzyme-linked immunospot assay. The Salmonella fimbrial display system was efficient at the induction of an antitumor cellular immune response in vivo, providing a new strategy for the development of efficient cancer vaccinations.

scholarly journals Presentation of viral antigen to class I major histocompatibility complex-restricted cytotoxic T lymphocyte. Recognition of an immunodominant influenza hemagglutinin site by cytotoxic T lymphocyte is independent of the position of the site in the hemagglutinin translation product.

1991 ◽  
Vol 174 (3) ◽  
pp. 733-736 ◽  
Author(s):  
Y S Hahn ◽  
V L Braciale ◽  
T J Braciale
Keyword(s):  
Major Histocompatibility Complex ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Antigenic Site ◽  
Class I ◽  
Translation Product ◽  
Coding Sequence ◽  
Histocompatibility Complex ◽  
Hemagglutinin Gene

Class I major histocompatibility complex (MHC) restricted T lymphocytes preferentially recognize fragments of polypeptides processed through a nonendosomal presentation pathway. At present the intracellular compartment(s) in which polypeptide fragmentation occurs and factors which influence the formation of an antigenic epitope are not well understood. To assess the role of residues flanking an antigenic site in the generation of the antigenic moiety recognized by class I MHC restricted T lymphocytes we have moved the coding sequence for an immunodominant H-2Kd restricted site on the influenza A/JAPAN/57 hemagglutinin (residues 202-221) by site-directed mutagenesis to six different positions along the coding sequence of the hemagglutinin gene. We have found that all six classes of mutants are recognized by MHC class I restricted T cells as efficiently as the wild type hemagglutinin gene product. Thus neither N-terminal to C-terminal position within the translation product nor sequences flanking the antigenic site influence processing.

Cytotoxic T lymphocyte recognition of the H-2-erbB hybrid gene product lacking the complete H-2 domain structure

1990 ◽  
Vol 2 (1) ◽  
pp. 91-97 ◽  
Author(s):  
L. Ding ◽  
K. Isobe ◽  
T. Iwamoto ◽  
T. Yoshida ◽  
F. Nagase ◽  
...  
Keyword(s):  
Gene Product ◽  
Domain Structure ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Hybrid Gene
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