scholarly journals T-cell-receptor cross-recognition and strategies to select safe T-cell receptors for clinical translation

2019 ◽  
Vol 2 ◽  
pp. 1-10 ◽  
Author(s):  
Amalie Kai Bentzen ◽  
Sine Reker Hadrup
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Receptors ◽  
Cell Receptor ◽  
Clinical Translation ◽  
Cell Receptors

Developing and validating an approach for diagnosing and prognosticating cancer from biochemical motifs in T-cell receptors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15260-e15260
Author(s):  
Jared L Ostmeyer ◽  
Lindsay G Cowell ◽  
Scott Christley
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
T Cell Receptor ◽  
T Cell Receptors ◽  
Ovarian Tissue ◽  
Cell Receptor ◽  
Healthy Tissue ◽  
Cervical Lesions ◽  
Cell Receptors ◽  
Biochemical Features

e15260 Background: Immune repertoire deep sequencing allows profiling T-cell populations and enables novel approaches to diagnose and prognosticate cancer by identifying T-cell receptor sequence patterns associated with clinical phenotypes and outcomes. Methods: Our goal is to develop a method to diagnose and prognosticate cancer using sequenced T-cell receptors. To determine how to profile the specificity of a T-cell receptor, we analyze 3D X-ray crystallographic structures of T-cell receptors bound to antigen. We observe a contiguous strip typically 4 amino acid residues in length from the complimentary determining region 3 (CDR3) lying in direct contact with the antigen. Based on this observation, we extract 4 residue long snippets from every receptor’s CDR3 and represent each snippet using biochemical features encoded by its amino acid sequence. The biochemical features are combined with information about the abundance of the snippet or the receptor and scored using a machine learning based approach. Each predictive model is fitted and validated under the requirement that at least one positively labelled snippet appears per tumor and no positively labelled snippets appear in healthy tissue. Results: Using a patient-holdout cross-validation, we fit predictive models to distinguish: 1. colorectal tumors from healthy tissue matched controls with 93% accuracy, 2. breast tumors from healthy tissue matched controls with 94% accuracy, 3. ovarian tumors from non-cancer patient ovarian tissue with 95% accuracy (80% accuracy on a blinded follow-up cohort) 4. and regression of preneoplastic cervical lesions over 1 year in advance with 96% accuracy. Conclusions: Immune repertoires can be used to diagnose and prognosticate cancer.

scholarly journals T Cell Receptor Transfection Shows Non-HLA-Restricted Recognition of Nickel by CD8+ Human T Cells to be Mediated by αβ T Cell Receptors

2003 ◽  
Vol 121 (3) ◽  
pp. 496-501 ◽  
Author(s):  
Corinne Moulon ◽  
Yoanna Choleva ◽  
Hermann-Josef Thierse ◽  
Doris Wild ◽  
Hans Ulrich Weltzien
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
T Cell Receptors ◽  
Cell Receptor ◽  
Cell Receptors ◽  
Human T Cells

T Cell Receptor CDR3 Sequences and Recombinant T Cell Receptors

1997 ◽  
Vol 113 (1-3) ◽  
pp. 170-172 ◽  
Author(s):  
Slawomir Sowka ◽  
Roswitha Friedl-Hajek ◽  
Ute Siemann ◽  
Christof Ebner ◽  
Otto Scheiner ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Receptors ◽  
Cell Receptor ◽  
Cell Receptors

scholarly journals The somatically generated portion of T cell receptor CDR3α contributes to the MHC allele specificity of the T cell receptor

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Philippa Marrack ◽  
Sai Harsha Krovi ◽  
Daniel Silberman ◽  
Janice White ◽  
Eleanor Kushnir ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Positive Selection ◽  
T Cell Receptor ◽  
T Cell Receptors ◽  
Cell Receptor ◽  
Structural Basis ◽  
Major Histocompatibility ◽  
Cell Receptors ◽  
Histocompatibility Complex

Mature T cells bearing αβ T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor β chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor α and β chain and, surprisingly, dramatically affected by the non germ line encoded portions of CDR3 of the T cell receptor α chain. Thus, in addition to determining specificity for antigen, the non germline encoded elements of T cell receptors may help the proteins cope with the extremely polymorphic nature of major histocompatibility complex products within the species.

scholarly journals Analysis of SARS-CoV-2 specific T-cell receptors in ImmuneCode reveals cross-reactivity to immunodominant Influenza M1 epitope

2020 ◽  
Author(s):  
John-William Sidhom ◽  
Alexander S. Baras
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Receptors ◽  
Cell Receptor ◽  
Cross Reactivity ◽  
Cell Receptors

Adaptive Biotechnologies and Microsoft have recently partnered to release ImmuneCode, a database containing SARS-CoV-2 specific T-cell receptors derived through MIRA, a T-cell receptor (TCR) sequencing based sequencing approach to identify antigen-specific TCRs. Herein, we query the extent of cross reactivity between these derived SARS-CoV-2 specific TCRs and other known antigens present in McPas-TCR, a manually curated catalogue of pathology-associated TCRs. We reveal cross reactivity between SARS-CoV-2 specific TCRs and the immunodominant Influenza GILGFVFTL M1 epitope, suggesting the importance of further work in characterizing the implications of prior Influenza exposure or co-exposure to the pathology of SARS-CoV-2 illness.

scholarly journals T cell receptor V-gene usage in oral lichen planus; increased frequency of T cell receptors expressing Vα2 and Vβ3

2008 ◽  
Vol 98 (3) ◽  
pp. 503-507 ◽  
Author(s):  
C. SIMARK-MATTSSON ◽  
G. BERGENHOLTZ ◽  
M. JONTELL ◽  
A. TARKOWSKI ◽  
U. I. DAHLGREN
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Lichen Planus ◽  
T Cell Receptors ◽  
Oral Lichen Planus ◽  
Cell Receptor ◽  
Cell Receptors ◽  
Gene Usage ◽  
V Gene ◽  
Oral Lichen

scholarly journals The Single Positive T Cells Found in CD3-ζ/η−/− Mice Overtly React with Self–Major Histocompatibility Complex Molecules upon Restoration of Normal Surface Density of T Cell Receptor–CD3 Complex

1997 ◽  
Vol 185 (4) ◽  
pp. 707-716 ◽  
Author(s):  
Shih-Yao Lin ◽  
Laurence Ardouin ◽  
Anne Gillet ◽  
Marie Malissen ◽  
Bernard Malissen
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
T Cell Receptors ◽  
Cell Receptor ◽  
Normal Density ◽  
Cell Receptors ◽  
Peripheral T Cells ◽  
Single Positive ◽  
Deficient Mice

CD3-ζ/η–deficient mice have small thymuses containing cells that show a profound reduction in the surface levels of T cell receptors and terminate their differentiation at the CD4+CD8+ stage. Rather unexpectedly, CD3− or very low single positive T cells accumulate over time in the spleen and lymph nodes of CD3-ζ/η–deficient mice after a process dependent on MHC expression. Fusion of these peripheral T cells with a CD3-ζ–positive derivative of the BW5147 TCR-α−/β− thymoma resulted in hybridomas that do express an heterogeneous set of T cell receptor α/β dimers at their surface and at density comparable to those found in hybridomas derived from wild-type peripheral T cells. We have investigated the specificities of these T cell receptors using spleen cells from congenic and mutant mouse strains, and showed that the majority of them readily recognized self-MHC class I or class II molecules. These results demonstrate that by increasing the density and/or output of the T cell receptors expressed in peripheral T cells, one can confer them with the capacity to respond to normal density of self-MHC molecules.

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