scholarly journals Tissue-specific T cell receptor (TCR) sequencing to evaluate immune response to therapeutic HPV vaccines

2014 ◽  
Vol 7 (8) ◽  
pp. 234-234
2004 ◽  
Vol 200 (11) ◽  
pp. 1371-1382 ◽  
Author(s):  
Dipica Haribhai ◽  
Brandon Edwards ◽  
Mary L. Williams ◽  
Calvin B. Williams

The T cell receptor must translate modest, quantitative differences in ligand binding kinetics into the qualitatively distinct signals used to determine cell fate. Here, we use mice that express an endogenous T cell receptor (TCR) antagonist and an adoptive transfer system to examine the influence of TCR signal quality on the development of effector function. We show that activation of antigen-specific T cells in the presence of an antagonist results in a functional reprogramming of the primary immune response, marked by altered T cell homing, a failure to develop effector function, and ultimately clonal elimination by apoptosis. Importantly, antagonism does not block cell division, implying that the signals promoting clonal expansion and effector differentiation are distinct.


2020 ◽  
Vol 38 (10) ◽  
pp. 1194-1202 ◽  
Author(s):  
Huang Huang ◽  
Chunlin Wang ◽  
Florian Rubelt ◽  
Thomas J. Scriba ◽  
Mark M. Davis

2006 ◽  
Vol 84 (2) ◽  
pp. 135-141 ◽  
Author(s):  
Xiaoyin Zhang ◽  
Liu Hong ◽  
W Y Chan ◽  
Taidong Qiao ◽  
Baojun Chen ◽  
...  

MG7-Ag is a human gastric-carcinoma-associated antigen with a high specificity. So far it is remained unclear whether MG7-Ag is correlated with the in vivo cellular immune response of patients with gastric cancer. In this study, we detected the expression of the T cell receptor (TCR) repertoire of T cell subpopulations and cytokines in tumor-infiltrating lymphocytes (TIL), peripheral blood lymphocytes (PBL), and residue benign mucosal lymphocytes (NML) of patients with gastric cancer using semiquantitative RT-PCR. Our data showed that the expanded clones in CD8+ NML and TIL and CD4+ NML and PBL in MG7-Ag-positive patients were significantly fewer than those of MG7-Ag-negative patients (p = 0.0360; p = 0.0026; p = 0.0065 p = 0.0109, respectively). The levels of IL-8 in CD8+ TIL and TNF in CD4+ TIL from the MG7-Ag-positive group were significantly higher than those from the MG7-Ag-negative group (p = 0.0302; p = 0.0177, respectively). Taken together, the results demonstrated a weaker T cell immune response and more proinflammatory cytokine secretion in MG7-Ag-positive patients with gastric cancer than in MG7-Ag-negative ones. This likely contributes to the poor prognosis in MG7-Ag-positive gastric-cancer patients.Key words: gastric carcinoma, tumor-associated antigen, T cell receptor repertoire, cytokine, RT-PCR.


2017 ◽  
Author(s):  
J. Textor ◽  
A. Fähnrich ◽  
M. Meinhardt ◽  
C. Tune ◽  
S. Klein ◽  
...  

Immunological differences between hosts, such as diverse T-cell receptor (TCR) repertoires, are widely credited for reducing the risk of pathogen spread and adaptation in a population. Within-host immunological diversity might likewise be important for robust pathogen control, but to what extent naïve TCR repertoires differ across different locations in the same host is unclear. T-cell zones (TCZs) in secondary lymphoid organs provide secluded micro-environmental niches. By harboring distinct TCRs, such niches could enhance within-host immunological diversity. On the other hand, rapid T cell migration is expected to dilute such diversity. Here, we combined tissue micro-dissection and deep sequencing of the TCR β chain to examine the extent to which TCR repertoires differ between TCZs in murine spleens. In the absence of antigen, we found little evidence for differences between different TCZs of the same spleen. Yet, three days after immunization with sheep red blood cells, we observed a >10-fold rise in the number of clones that appeared to localize to individual zones. Remarkably, these differences largely disappeared at 4 days after immunization, when hallmarks of an ongoing immune response were still observed. These data suggest that in the absence of antigen, any repertoire differences observed between TCZs of the same host can largely be attributed to random clone distribution. Upon antigen challenge, segregated TCR compartments appear and disappear within days. Such “transient mosaic” dynamics could be an important barrier for pathogen adaptation and spread during an immune response.


2021 ◽  
Author(s):  
Kevin Mohammed ◽  
Austin Meadows ◽  
Sandra Hatem ◽  
Viviana Simon ◽  
Anitha D Jayaprakash ◽  
...  

Early, high-resolution metrics are needed to ascertain the immune response to vaccinations. The T cell receptor (TCR), a heterodimer of one α and one β chain, is a promising target, with the complete TCR repertoire reflecting the T cells present in an individual. To this end, we developed Tseek, an unbiased and accurate method for profiling the TCR repertoire by sequencing the TCR α and β chains and developing a suite of tools for repertoire analysis. An added advantage is the ability to non-invasively analyze T cells in peripheral blood mononuclear cells (PBMCs). Tseek and the analytical suite were used to explore the T cell response to both the COVID-19 mRNA vaccine (n=9) and the seasonal inactivated Influenza vaccine (n=5) at several time points. Neutralizing antibody titers were also measured in the covid vaccine samples. The COVID-19 vaccine elicited a broad T cell response involving multiple expanded clones, whereas the Influenza vaccine elicited a narrower response involving fewer clones. Many distinct T cell clones responded at each time point, over a month, providing temporal details lacking in the antibody measurements, especially before the antibodies are detectable. In individuals recovered from a SARS-CoV-2 infection, the first vaccine dose elicited a robust T cell response, while the second dose elicited a comparatively weaker response, indicating a saturation of the response. The physical symptoms experienced by the recipients immediately following the vaccinations were not indicative of the TCR/antibody responses, while a weak TCR response seemed to presage a weak antibody response. We also found that the TCR repertoire acts as an individual fingerprint: donors of blood samples taken years apart could be identified solely based upon their TCR repertoire, hinting at other surprising uses the TCR repertoire may have. These results demonstrate the promise of TCR repertoire sequencing as an early and sensitive measure of the adaptive immune response to vaccination, which can help improve immunogen selection and optimize vaccine dosage and spacing between doses.


Author(s):  
Sean Nolan ◽  
Marissa Vignali ◽  
Mark Klinger ◽  
Jennifer N. Dines ◽  
Ian M. Kaplan ◽  
...  

Abstract We describe the establishment and current content of the ImmuneCODE™ database, which includes hundreds of millions of T-cell Receptor (TCR) sequences from over 1,400 subjects exposed to or infected with the SARS-CoV-2 virus, as well as over 135,000 high-confidence SARS-CoV-2-specific TCRs. This database is made freely available, and the data contained in it can be downloaded and analyzed online or offline to assist with the global efforts to understand the immune response to the SARS-CoV-2 virus and develop new interventions.


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