Antigen specificity of semi‐invariant CD1d‐restricted T cell receptors: The best of both worlds?

2004 ◽  
Vol 82 (3) ◽  
pp. 285-294 ◽  
Author(s):  
Jenny E Gumperz
Keyword(s):  
T Cell ◽  
T Cell Receptors ◽  
Antigen Specificity ◽  
Cell Receptors

Recovery of Paired T Cell Receptors from Single-cell Seq-Well Libraries

2019 ◽  
Author(s):  
Ang A. Tu ◽  
Todd M. Gierahn ◽  
Brinda Monian ◽  
Duncan M. Morgan ◽  
Naveen K. Mehta ◽  
...  
Keyword(s):  
T Cells ◽  
Food Allergy ◽  
T Cell ◽  
Single Cell ◽  
T Cell Receptors ◽  
Immune Cell ◽  
Cost Effective ◽  
Antigen Specificity ◽  
Activated T Cells ◽  
Cell Receptors

Abstract High-throughput 3’ single-cell RNA-Sequencing (scRNA-Seq) allows for cost-effective, detailed characterization of thousands of individual immune cells from healthy and diseased tissues. Current techniques, however, are limited in their ability to elucidate essential immune cell features, including the variable sequences of T cell receptors (TCRs) that confer antigen specificity in T cells. Here, we present an enrichment strategy that enables simultaneous analysis of TCR variable sequences and corresponding full transcriptomes from 3’ barcoded scRNA-Seq samples. This approach is compatible with common 3’ scRNA-Seq methods, and adaptable to processed samples post hoc. We applied the technique to resolve clonotype-to-phenotype relationships among antigen-activated T cells from immunized mice and from patients with food allergy. We observed diverse but preferential cellular phenotypes manifest among subsets of expanded clonotypes, including functional Th2 states associated with food allergy. These results demonstrate the utility of our method when studying complex diseases in which clonotype-driven immune responses are critical to understanding the underlying biology.

scholarly journals Predicting Cross-Reactivity and Antigen Specificity of T Cell Receptors

2020 ◽  
Vol 11 ◽  
Author(s):  
Chloe H. Lee ◽  
Mariolina Salio ◽  
Giorgio Napolitani ◽  
Graham Ogg ◽  
Alison Simmons ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptors ◽  
Cross Reactivity ◽  
Antigen Specificity ◽  
Cell Receptors

scholarly journals TCR3d: The T cell receptor structural repertoire database

2019 ◽  
Vol 35 (24) ◽  
pp. 5323-5325 ◽  
Author(s):  
Ragul Gowthaman ◽  
Brian G Pierce
Keyword(s):  
T Cell ◽  
T Cell Receptors ◽  
Adaptive Immune System ◽  
Cell Receptor ◽  
Binding Mode ◽  
Computational Techniques ◽  
Antigen Specificity ◽  
Cell Receptors ◽  
Gene Usage ◽  
Mechanistic Basis

Abstract Summary T cell receptors (TCRs) are critical molecules of the adaptive immune system, capable of recognizing diverse antigens, including peptides, lipids and small molecules, and represent a rapidly growing class of therapeutics. Determining the structural and mechanistic basis of TCR targeting of antigens is a major challenge, as each individual has a vast and diverse repertoire of TCRs. Despite shared general recognition modes, diversity in TCR sequence and recognition represents a challenge to predictive modeling and computational techniques being developed to predict antigen specificity and mechanistic basis of TCR targeting. To this end, we have developed the TCR3d database, a resource containing all known TCR structures, with a particular focus on antigen recognition. TCR3d provides key information on antigen binding mode, interface features, loop sequences and germline gene usage. Users can interactively view TCR complex structures, search sequences of interest against known structures and sequences, and download curated datasets of structurally characterized TCR complexes. This database is updated on a weekly basis, and can serve the community as a centralized resource for those studying T cell receptors and their recognition. Availability and implementation The TCR3d database is available at https://tcr3d.ibbr.umd.edu/.

scholarly journals Needle in a Haystack: The Naïve Repertoire as a Source of T Cell Receptors for Adoptive Therapy with Engineered T Cells

2020 ◽  
Vol 21 (21) ◽  
pp. 8324 ◽  
Author(s):  
Elvira D’Ippolito ◽  
Karolin I. Wagner ◽  
Dirk H Busch
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
T Cell Receptors ◽  
Adoptive T Cell Therapy ◽  
Patient Specific ◽  
Antigen Specificity ◽  
Adoptive Therapy ◽  
T Cell Therapy ◽  
Cell Receptors

T cell engineering with antigen-specific T cell receptors (TCRs) has allowed the generation of increasingly specific, reliable, and versatile T cell products with near-physiological features. However, a broad applicability of TCR-based therapies in cancer is still limited by the restricted number of TCRs, often also of suboptimal potency, available for clinical use. In addition, targeting of tumor neoantigens with TCR-engineered T cell therapy moves the field towards a highly personalized treatment, as tumor neoantigens derive from somatic mutations and are extremely patient-specific. Therefore, relevant TCRs have to be de novo identified for each patient and within a narrow time window. The naïve repertoire of healthy donors would represent a reliable source due to its huge diverse TCR repertoire, which theoretically entails T cells for any antigen specificity, including tumor neoantigens. As a challenge, antigen-specific naïve T cells are of extremely low frequency and mostly of low functionality, making the identification of highly functional TCRs finding a “needle in a haystack.” In this review, we present the technological advancements achieved in high-throughput mapping of patient-specific neoantigens and corresponding cognate TCRs and how these platforms can be used to interrogate the naïve repertoire for a fast and efficient identification of rare but therapeutically valuable TCRs for personalized adoptive T cell therapy.

scholarly journals Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition

1981 ◽  
Vol 153 (5) ◽  
pp. 1198-1214 ◽  
Author(s):  
JW Kappler ◽  
B Skidmore ◽  
J White ◽  
P Marrack
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptors ◽  
Interleukin 2 ◽  
Specific Antigen ◽  
Antigen Specificity ◽  
Cell Receptors ◽  
Cell Hybrids

We developed a method for production of antigen-specific, H-2-restricted T cell hybrids. The tumor cell partner in the fusions was itself a T cell hybrid, FS6-14.13.AG2 (or its derivatives), which could be induced to produce the growth factor, interleukin-2 (IL-2), in response to a challenge with concanavalin A, but had no known antigen specificity. The normal T cell partner in the fusions was a population of lymph node T cell blasts that had been highly enriched in antigen-specific, H-2-restricted T cells by in vivo immunization, followed by in vitro challenge with antigen and clonal expansion in IL-2-containing medium. These fusions produced hybrids that grew constitutively in culture. A sizable proportion of the hybrids demonstrated the ability to produce IL-2 in response to a challenge with specific antigen presented by irradiated spleen cells of the appropriate H-2 type. Four cloned antigen/H-2-specific hybrid lines were produced. AO-40.10 responded to chicken ovalbumin (OVA) when presented by I-A(k)-bearing cells. DC1.18.3 responded to the apo form of beef cytochrome c when presented with I-A(d). AODK-10.4 responded to keyhole limpet hemocyanin (KLH) presented with I-A (d). AODK-1.16 also responded to KLH presented by a product of the I region of H-2(d), but the data were consistent with either a product of the I-J-I-E(d) region or a combinatorial molecule with elements from both I-A(d) and I-E(d)/I-C(d). Coincidentally, AO-40.10 was shown to have an unexpected alloreactivity with a product of H-2(b) mapping to the K-I-A region. These hybrids should prove invaluable as sources of monoclonal material for the study of the receptor(s) on T cells with H-2-restricted antigen specificities. We also generated T cell hybrids with two antigen/H-2 specificities by fusing an azaguanine-resistant clone of AO-40.10 to normal T cells with a different antigen/H-2 specificity. Many of the hybrids retained reactivity to OVA plus H-2(a) and to the second antigen/H-2 combination. None reacted to either OVA plus the second H-2 type or to the second antigen plus H-2(a). One of these hybrids was successfully cloned to produce the line AOFK- 11.11.1. It retained the ability to recognize OVA plus I-A(k) inherited from one parent, and KLH plus IA(f) inherited from the other. It did not recognize OVA plus IA(f) or KLH plus I-A(k). These results have some bearing on models describing the nature of T cell receptors for antigen recognized in association with H-2 products. They do not support models in which antigen and H-2 are recognized separately by two independent T cell receptors.

How Far we are towards Eradication of HBV Infection

2015 ◽  
Vol 24 (4) ◽  
pp. 473-479 ◽  
Author(s):  
Mihai Voiculescu
Keyword(s):  
Immune Response ◽  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
T Cell Receptors ◽  
Hepatitis B Surface Antigen ◽  
Hbv Infection ◽  
Major Health Problem ◽  
Cell Receptors ◽  
B Virus

Hepatitis B virus (HBV) infection is a major health problem with an important biological and a significant socio-economic impact all over the world. There is a high pressure to come up with a new and more efficient strategy against HBV infection, especially after the recent success of HCV treatment. Preventing HBV infection through vaccine is currently the most efficient way to decrease HBV-related cirrhosis and liver cancer incidence, as well as the best way to suppress the HBV reservoir. The vaccine is safe and efficient in 80-95% of cases. One of its most important roles is to reduce materno-fetal transmission, by giving the first dose of vaccine in the first 24 hours after birth. Transmission of HBV infection early in life is still frequent, especially in countries with high endemicity.Successful HBV clearance by the host is immune-mediated, with a complex combined innate and adaptive cellular and humoral immune response. Different factors, such as the quantity and the sequence of HBV epitope during processing by dendritic cells and presenting by different HLA molecules or the polymorphism of T cell receptors (TOL) are part of a complex network which influences the final response. A new potential therapeutic strategy is to restore T-cell antiviral function and to improve innate and adaptive immune response by immunotherapeutic manipulation.It appears that HBV eradication is far from being completed in the next decades, and a new strategy against HBV infection must be considered. Abbreviations: ALT: alanine aminotransferase; APC: antigen presenting cells; cccDNA: covalently closed circular DNA; HBIG: hepatitis B immunoglobulin; HbsAg: hepatitis B surface antigen; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; CTL: cytotoxic T lymphocyte; IFN: interferon; NUC: nucleos(t)ide analogues; pg RNA: pre genomic RNA; TLR: toll-like receptors; TOL: T cell receptors.

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