Autoimmune T cell recognition of alternative-reading-frame-encoded peptides

2017 ◽  
Vol 23 (4) ◽  
pp. 409-410 ◽  
Author(s):  
Jiajie Wei ◽  
Jonathan W Yewdell
2004 ◽  
Vol 78 (19) ◽  
pp. 10460-10469 ◽  
Author(s):  
Christine Bain ◽  
Peggy Parroche ◽  
Jean Pierre Lavergne ◽  
Blandine Duverger ◽  
Claude Vieux ◽  
...  

ABSTRACT In vitro studies have described the synthesis of an alternative reading frame form of the hepatitis C virus (HCV) core protein that was named F protein or ARFP (alternative reading frame protein) and includes a domain coded by the +1 open reading frame of the RNA core coding region. The expression of this protein in HCV-infected patients remains controversial. We have analyzed peripheral blood from 47 chronically or previously HCV-infected patients for the presence of T lymphocytes and antibodies specific to the ARFP. Anti-ARFP antibodies were detected in 41.6% of the patients infected with various HCV genotypes. Using a specific ARFP 99-amino-acid polypeptide as well as four ARFP predicted class I-restricted 9-mer peptides, we show that 20% of the patients display specific lymphocytes capable of producing gamma interferon, interleukin-10, or both cytokines. Patients harboring three different viral genotypes (1a, 1b, and 3) carried T lymphocytes reactive to genotype 1b-derived peptides. In longitudinal analysis of patients receiving therapy, both core and ARFP-specific T-cell- and B-cell-mediated responses were documented. The magnitude and kinetics of the HCV antigen-specific responses differed and were not linked with viremia or therapy outcome. These observations provide strong and new arguments in favor of the synthesis, during natural HCV infection, of an ARFP derived from the core sequence. Moreover, the present data provide the first demonstration of the presence of T-cell-mediated immune responses directed to this novel HCV antigen.


Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5390
Author(s):  
Dyantha I. van der Lee ◽  
Georgia Koutsoumpli ◽  
Rogier M. Reijmers ◽  
Willy Honders ◽  
Rob C. M. de Jong ◽  
...  

Acute myeloid leukemia (AML) is a hematological malignancy caused by clonal expansion of myeloid progenitor cells. Most patients with AML respond to chemotherapy, but relapses often occur and infer a very poor prognosis. Thirty to thirty-five percent of AMLs carry a four base pair insertion in the nucleophosmin 1 gene (NPM1) with a C-terminal alternative reading frame of 11 amino acids. We previously identified various neopeptides from the alternative reading frame of mutant NPM1 (dNPM1) on primary AML and isolated an HLA-A*02:01-restricted T-cell receptor (TCR) that enables human T-cells to kill AML cells upon retroviral gene transfer. Here, we isolated T-cells recognizing the dNPM1 peptide AVEEVSLRK presented in HLA-A*11:01. The TCR cloned from a T-cell clone recognizing HLA-A*11:01+ primary AML cells conferred in vitro recognition and lysis of AML upon transfer to CD8 cells, but failed to induce an anti-tumor effect in immunodeficient NSG mice engrafted with dNPM1 OCI-AML3 cells. In conclusion, our data show that AVEEVSLRK is a dNPM1 neoantigen on HLA-A*11:01+ primary AMLs. CD8 cells transduced with an HLA-A*11:01-restricted TCR for dNPM1 were reactive against AML in vitro. The absence of reactivity in a preclinical mouse model requires further preclinical testing to predict the potential efficacy of this TCR in clinical development.


2010 ◽  
Vol 60 (1) ◽  
pp. 133-144 ◽  
Author(s):  
Timothy J. Haggerty ◽  
Ian S. Dunn ◽  
Lenora B. Rose ◽  
Estelle E. Newton ◽  
Sunil Martin ◽  
...  

1976 ◽  
Vol 144 (4) ◽  
pp. 1134-1140 ◽  
Author(s):  
T G Rehn ◽  
J K Inman ◽  
G M Shearer

The specificity of C57BL/10 cytotoxic effector cells generated by in vitro sensitization with autologous spleen cells modified with a series of related nitrophenyl compounds was investigated. The failure of trinitrophenyl (TNP)-sensitized effector cells to lyse TNP-beta-alanylglycylglycyl(AGG)-modified target cells is presented as evidence contradicting the intimacy or dual receptor model or T-cell recognition in its simplest form. Data are also shown indicating that sensitization with N-(3-nitro-4-hydroxy-5-iodophenylacetyl)-AGG-modified stimulating cells generates noncross-reacting clones of cytotoxic effector cells.


1993 ◽  
Vol 23 (s1) ◽  
pp. 11-11
Author(s):  
Paul J Fairchild ◽  
David C Wraith

2012 ◽  
Vol 42 (11) ◽  
pp. 2990-3000 ◽  
Author(s):  
Eva B. Allerbring ◽  
Adil D. Duru ◽  
Hannes Uchtenhagen ◽  
Chaithanya Madhurantakam ◽  
Markus B. Tomek ◽  
...  

2006 ◽  
Vol 121 (2) ◽  
pp. 134-143 ◽  
Author(s):  
Massimo Amicosante ◽  
Andrew P. Fontenot

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