scholarly journals +1 Frameshifting as a Novel Mechanism to Generate a Cryptic Cytotoxic T Lymphocyte Epitope Derived from Human Interleukin 10

2002 ◽  
Vol 195 (3) ◽  
pp. 353-358 ◽  
Author(s):  
Xavier Saulquin ◽  
Emmanuel Scotet ◽  
Lydie Trautmann ◽  
Marie-Alix Peyrat ◽  
Franck Halary ◽  
...  
Keyword(s):  
Cytotoxic T Lymphocyte ◽  
Cell Clone ◽  
Cytotoxic T Cells ◽  
Interleukin 10 ◽  
Site Directed Mutagenesis ◽  
Dna Encoding ◽  
Reading Frame ◽  
Autoreactive T Cell ◽  
T Cell Clone ◽  
Cryptic Epitopes

Recent data indicate that some cytotoxic T cells (CTLs) recognize so-called cryptic epitopes, encoded by nonprimary open reading frame (ORF) sequences or other nonclassical expression pathways. We describe here a novel mechanism leading to generation of a cryptic CTL epitope. We isolated from the synovial fluid of a patient suffering from a Reiter's syndrome an autoreactive T cell clone that recognized cellular IL-10 in the HLA-B*2705 context. The minimal IL-10 sequence corresponding to nucleotides 379–408 was shown to activate this clone, upon cotransfection into COS cells with the DNA encoding HLA-B*2705, but the synthetic peptide deduced from this sequence did not stimulate the clone. Using a site-directed mutagenesis approach, we found that this clone recognized a transframe epitope generated by an internal +1 frameshifting in the IL-10 sequence and so derived partly from ORF1, partly from ORF2. We defined that +1 frameshifting was induced by a specific heptamer sequence. These observations illustrate the variety of mechanisms leading to generation of cryptic epitopes and suggest that frameshifting in normal cellular genes may be more common than expected.

αs1-Casein-specific CD8+T Cell Clone That Inhibits Its Own Interferon-γProduction by Producing Interleukin-10

1995 ◽  
Vol 59 (12) ◽  
pp. 2274-2276 ◽  
Author(s):  
Ken-ichi Nishijima ◽  
Tatsuhiro Hisatsune ◽  
Hiroko Kato ◽  
Osamu Shiho ◽  
Shuichi Kaminogawa
Keyword(s):  
T Cell ◽  
Cell Clone ◽  
Cd8 T Cell ◽  
Interleukin 10 ◽  
T Cell Clone

scholarly journals MHC-restricted minimal regulatory circuit initiated by a class II-autoreactive T cell clone.

1987 ◽  
Vol 165 (5) ◽  
pp. 1284-1295 ◽  
Author(s):  
K Sano ◽  
I Fujisawa ◽  
R Abe ◽  
Y Asano ◽  
T Tada
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Clone ◽  
Class Ii ◽  
Secondary Antibody ◽  
Th Cells ◽  
Mhc Restriction ◽  
Autoreactive T Cell ◽  
Regulatory Circuit ◽  
T Cell Clone

The in vivo administration of a self-class II-reactive Th clone MS202 derived from C3H into syngeneic mice resulted in the suppression of both primary and early secondary antibody responses against T cell-dependent antigens. The suppression was due to the generation of antigen-nonspecific Ts cells in the recipient, as the splenic T cells from the mice treated with MS202 were able to strongly suppress the in vitro secondary antibody response of primed syngeneic spleen cells. The dose-response curve of suppression indicated the generation of an effector type Ts that directly suppressed Th. The surface phenotype of Ts was Ly-1+,2-, L3T4+, I-J-. The presence of Ly-1+,2+ T cells was not required to induce the suppression. The suppression was strictly restricted to H-2k, as F1 Ts cells were able to suppress the response of C3H but not of B6 B cells helped by the same F1 Th cells. The experiments with chimeric mice indicated that the direct target of Ts is an MHC-restricted Th but not a B cell or APC. The results indicate the existence of a minimal regulatory circuit where an MHC-restricted Th induces a preprogrammed Ts that in turn directly suppresses Th with the same MHC-restriction specificity. The induction of and suppression by Ts appeared to be due to the direct recognition of MHC restriction sites of Th cells.

OKT4 monoclonal antibody-induced activation of an autoreactive T-cell clone

1989 ◽  
Vol 123 (1) ◽  
pp. 244-252 ◽  
Author(s):  
Constantin G. Ioannides ◽  
Ralph S. Freedman ◽  
Chris D. Platsoucas
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Cell Clone ◽  
Autoreactive T Cell ◽  
T Cell Clone

scholarly journals Identification of TCR repertoires in functionally competent cytotoxic T cells cross-reactive to SARS-CoV-2

2021 ◽  
Author(s):  
Kanako Shimizu ◽  
Tomonori Iyoda ◽  
An Sanpei ◽  
Hiroshi Nakazato ◽  
Masahiro Okada ◽  
...  
Keyword(s):  
T Cells ◽  
Vaccine Development ◽  
Cell Clone ◽  
Cytotoxic T Cells ◽  
Cell Level ◽  
Human Coronavirus ◽  
Healthy Donors ◽  
T Cell Clone ◽  
Selective Diversity ◽  
Dominant Epitope

Abstract SARS-CoV-2-specific CD8+ T cells are detectable in infected individuals but are low in unexposed healthy donors (UHD). Little is known about whether pre-existing human coronavirus (HCoV)-specific CD8+ T cells are converted to functionally competent T cells cross-reactive to SARS-CoV-2. Induction of cross-reactive immunity requires the recognition of multiple epitopes. Here, we show that SARS-CoV-2-specific T cells elicited in response to a selected dominant epitope are multifunctional and respond to various HCoVs in UHD. TCRαβ chains from each T cell clone were identified; TCRαβ-transduced T cells responded broadly to the relevant epitopes on several HCoVs, thus implying that TCRαβ may exhibit selective diversity at the single-cell level. We further defined four sets of optimal SARS-CoV-2-peptides and demonstrated the response of CD8+ T cells even in hematological malignant patients. Together, the proposed epitopes inducing pre-existing CD8+ T cells to cross-react with SARS-CoV-2 may be beneficial in vaccine development.

scholarly journals In Vivo Survival of  Viral Antigen–specific T Cells that Induce Experimental Autoimmune Encephalomyelitis

1998 ◽  
Vol 188 (9) ◽  
pp. 1725-1738 ◽  
Author(s):  
Rafael L. Ufret-Vincenty ◽  
Laura Quigley ◽  
Nancy Tresser ◽  
Seong Hee Pak ◽  
Ameer Gado ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Viral Antigen ◽  
Low Dose ◽  
Cell Clone ◽  
Viral Peptide ◽  
Autoreactive T Cell ◽  
T Cell Clone

A peptide derived from the human papillomavirus L2 protein is recognized by a myelin basic protein (MBP)-specific T cell clone from a multiple sclerosis patient and by MBP-specific autoantibodies purified from multiple sclerosis brain tissue. We now show in mice that low doses of this papillomavirus peptide were optimal in selecting a subpopulation of papillomavirus peptide–specific T cells that cross-reacted with MBP(87–99) and with an unrelated viral peptide derived from the BSLF1 protein of Epstein-Barr virus (EBV). These low dose viral peptide– specific T cell lines were highly encephalitogenic. Splenocytes from mice transferred with viral peptide–specific T cells showed a vigorous response to both the papillomavirus and MBP peptides, indicating that viral antigen–specific T cells survived for a prolonged time in vivo. The EBV peptide, unable to prime and select an autoreactive T cell population, could still activate the low dose papillomavirus peptide–specific cells and induce central nervous system (CNS) autoimmunity. Cytokine profiles of papillomavirus peptide–specific encephalitogenic T cells and histopathology of CNS lesions resembled those induced by MBP. These results demonstrate conserved aspects in the recognition of the self-antigen and a cross-reactive viral peptide by human and murine MBP-specific T cell receptors. We demonstrate that a viral antigen, depending on its nature, dose, and number of exposures, may select autoantigen-specific T cells that survive in vivo and can trigger autoimmune disease after adoptive transfer.

scholarly journals A Processed Pseudogene Codes for a New Antigen Recognized by a Cd8+ T Cell Clone on Melanoma

2000 ◽  
Vol 191 (9) ◽  
pp. 1617-1624 ◽  
Author(s):  
Agnès Moreau-Aubry ◽  
Soizic Le Guiner ◽  
Nathalie Labarrière ◽  
Marie-Claude Gesnel ◽  
Francine Jotereau ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Clone ◽  
Stop Codon ◽  
Antigenic Peptides ◽  
Similar Sequence ◽  
Reading Frame ◽  
Gene Coding ◽  
Short Open Reading Frame ◽  
T Cell Clone ◽  
Processed Pseudogene

The M88.7 T cell clone recognizes an antigen presented by HLA B*1302 on the melanoma cell line M88. A cDNA encoding this antigen (NA88-A) was isolated using a library transfection approach. Analysis of the genomic gene's sequence identified it is a processed pseudogene, derived from a retrotranscript of mRNA coding for homeoprotein HPX42B. The NA88-A gene exhibits several premature stop codons, deletions, and insertions relative to the HPX42B gene. In NA88-A RNA, a short open reading frame codes for the peptide MTQGQHFLQKV from which antigenic peptides are derived; a stop codon follows the peptide's COOH-terminal Val codon. Part of the HPX42B mRNA's 3′ untranslated region codes for a peptide of similar sequence (MTQGQHFSQKV). If produced, this peptide can be recognized by M88.7 T cells. However, in HPX42B mRNA, the peptide's COOH-terminal Val codon is followed by a Trp codon. As a result, expression of HPX42B mRNA does not lead to antigen production. A model is proposed for events that participated in creation of a gene coding for a melanoma antigen from a pseudogene.

scholarly journals Human Paramyxovirus Infections Induce T Cells That Cross-React with Zoonotic Henipaviruses

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Rory D. de Vries ◽  
Alwin de Jong ◽  
R. Joyce Verburgh ◽  
Lucie Sauerhering ◽  
Gijsbert P. van Nierop ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Measles Virus ◽  
Cell Clone ◽  
Cytotoxic T Cells ◽  
Nipah Virus ◽  
Cell Epitope ◽  
Virus Infections ◽  
Human T Cell ◽  
T Cell Clone

ABSTRACT Humans are infected with paramyxoviruses of different genera early in life, which induce cytotoxic T cells that may recognize conserved epitopes. This raises the question of whether cross-reactive T cells induced by antecedent paramyxovirus infections provide partial protection against highly lethal zoonotic Nipah virus infections. By characterizing a measles virus-specific but paramyxovirus cross-reactive human T cell clone, we discovered a highly conserved HLA-B*1501-restricted T cell epitope in the fusion protein. Using peptides, tetramers, and single cell sorting, we isolated a parainfluenza virus-specific T cell clone from a healthy adult and showed that both clones cleared Nipah virus-infected cells. We identified multiple conserved hot spots in paramyxovirus proteomes that contain other potentially cross-reactive epitopes. Our data suggest that, depending on HLA haplotype and history of paramyxovirus exposures, humans may have cross-reactive T cells that provide protection against Nipah virus. The effect of preferential boosting of these cross-reactive epitopes needs to be further studied in light of paramyxovirus vaccination studies. IMPORTANCE Humans encounter multiple paramyxoviruses early in life. This study shows that infection with common paramyxoviruses can induce T cells cross-reactive with the highly pathogenic Nipah virus. This demonstrates that the combination of paramyxovirus infection history and HLA haplotype affects immunity to phylogenetically related zoonotic paramyxoviruses.

scholarly journals The interaction between CD8+ cytotoxic T cells and Leishmania-infected macrophages.

1991 ◽  
Vol 174 (3) ◽  
pp. 499-505 ◽  
Author(s):  
L E Smith ◽  
M Rodrigues ◽  
D G Russell
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Clone ◽  
Cytotoxic T Cells ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
T Cell Clone ◽  
Vitro Model ◽  
Leishmania Parasites

Leishmania is resident within the macrophages of its vertebrate host. In any intramacrophage infection, where the pathogen is present in a form capable of mediating cell to cell transmission, the contribution of a cytotoxic T cell response to protective immunity is questionable. This study presents data from an in vitro model designed to elucidate the outcome of an interaction between CD8+, cytotoxic T cells and infected macrophages. Experiments were conducted with an H-2d-restricted, cytotoxic CD8+ T cell clone and Leishmania parasites present in mixed macrophage cultures, with the parasites confined to either histocompatible BALB/c macrophages, or incompatible CBA macrophages. Initial experiments indicated that the viability of Leishmania was unaffected by the lysis of its host macrophage by cytotoxic T cells. However, extended experiments showed that the parasites were killed between 24 and 72 h. The same results were obtained regardless of whether the parasites were resident in the target, BALB/c, macrophages or the bystander, CBA, macrophages. Addition of neutralizing, anti-IFN-g antibody to the cultures ablated most of the leishmanicidal behavior, indicating that parasite death was attributable to macrophage activation, resulting from cytokine secretion from the T cells following the initial recognition event.

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