T‐cell receptor and B‐cell receptor repertoire profiling in adaptive immunity

Minervina, Anastasia A.; Pogorelyy, Mikhail V.; Mamedov, Ilgar Z.

doi:10.1111/tri.13475

Cited by 55 publications

(38 citation statements)

References 148 publications

(184 reference statements)

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“…between the naive, memory, effector memory, etc. phenotypes, which can obtained by flow-sorting cells before sequencing [22]. Another possible application would be to track the clones across different tissues and organs, and detect migrations and local expansions [23].…”

Section: Discussionmentioning

confidence: 99%

Inferring the immune response from repertoire sequencing

2020

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High-throughput sequencing of Band T-cell receptors makes it possible to track immune repertoires across time, in different tissues, and in acute and chronic diseases or in healthy individuals. However, quantitative comparison between repertoires is confounded by variability in the read count of each receptor clonotype due to sampling, library preparation, and expression noise. Here, we present a general Bayesian approach to disentangle repertoire variations from these stochastic effects. Using replicate experiments, we first show how to learn the natural variability of read counts by inferring the distributions of clone sizes as well as an explicit noise model relating true frequencies of clones to their read count. We then use that null model as a baseline to infer a model of clonal expansion from two repertoire time points taken before and after an immune challenge. Applying our approach to yellow fever vaccination as a model of acute infection in humans, we identify candidate clones participating in the response.

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Section: Discussionmentioning

confidence: 99%

Inferring the immune response from repertoire sequencing

2020

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“…Adaptive immune recognition of a diverse array of antigens is mediated by the structural diversity of B and T cell receptors -attributable to somatic hypermutation in V-region genes, and junctional and combinatorial diversity generated during gene rearrangement in B and T cells, respectively. 27 Conversely, the innate immune system comprising complement system, dendritic cells (DC), natural killer (NK) cells, macrophages, leucocytes and γδ T cells, is an older, evolutionarily conserved system that serves to prevent the spread and movement of foreign pathogens.…”

Section: Introductionmentioning

confidence: 99%

<p>Toll-Like Receptor 9 Agonists in Cancer</p>

Karapetyan

Luke

Davar

2020

OTT

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Toll-like receptor 9 (TLR9) is a pattern recognition receptor that is predominantly located intracellularly in immune cells, including dendritic cells, macrophages, natural killer cells, and other antigen-presenting cells (APC). The primary ligands for TLR9 receptors are unmethylated cytidine phosphate guanosine (CpG) oligodinucleotides (ODN). TLR9 agonists induce inflammatory processes that result in the enhanced uptake and killing of microorganisms and cancer cells as well as the generation of adaptive immune responses. Preclinical studies of TLR9 agonists suggested efficacy both as monotherapy and in combination with several agents, which led to clinical trials in patients with advanced cancer. In these studies, intravenous, intratumoral, and subcutaneous routes of administration have been tested; with anti-tumor responses in both treated and untreated metastatic sites. TLR9 agonist monotherapy is safe, although efficacy is minimal in advanced cancer patients; conversely, combinations appear to be more promising. Several ongoing phase I and II clinical trials are evaluating TLR9 agonists in combination with a variety of agents including chemotherapy, radiotherapy, targeted therapy, and immunotherapy agents. In this review article, we describe the distribution, structure and signaling of TLR9; discuss the results of preclinical studies of TLR9 agonists; and review ongoing clinical trials of TLR9 agonists singly and in combination in patients with advanced solid tumors.

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“…anti-Pd-1 mabs function by regulating the adaptive immune response (10), the selectivity of which derives from the enormous diversity of Tcrs and B cell receptors (Bcrs) (12). it is commonly known that anti-Pd-1 treatment can activate tumor-specific T cells by blocking the immune suppressive Pd-1 pathway.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive investigation of T and B cell receptor repertoires in an MC38 tumor model following murine anti‑PD‑1 administration

et al. 2020

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The Mc38 (derived from carcinogen-induced colon adenocarcinoma) tumor model is sensitive to anti-programmed cell death-1 (anti-Pd-1) treatment. However, there is no comprehensive description of the T and B cell receptor (Tcr, Bcr) repertoires of the Mc38 tumor model following anti-Pd-1 treatment, an improved understanding of which is highly important in the development of anti-Pd-1 immunotherapy. The present study analyzed the Tcr and Bcr repertoires of three types of tissue, including tumor, spleen and tumor draining lymph node (dln) from 20 Mc38 syngeneic mice receiving murine anti-Pd-1 (mdX400) treatment or mouse immunoglobulin G1 (migG1) control treatment. To obtain enough tissues for high-throughput sequencing, samples were collected on day 8 after the start of initial treatment. The usage frequencies of seven Tcr β chain (TrB) V genes and one TrBJ gene were significantly different between mDX400-and mIgG1-group tumors. Tcr repertoire diversity was significantly lower in mdX400-group tumors compared with migG1-group tumors, with the top 10 most frequent Tcr clonotypes notably expanded in mdX400-group tumors. in addition, the proportion of high-frequency Tcr clonotypes from mdX400-group tumors that were also present both in the dln and spleen was significantly higher than that in mIgG1-group tumors. Among the highly expanded Tcr clonotypes, one Tcr clonotype was consistently expanded in >50% of the mdX400-group tumors compared with migG1-group tumors. Similarly, one Bcr clonal family was highly expanded in >50% of mdX400-group tumor samples. The consistently expanded Tcr and Bcr clones were co-expanded in 29% of mdX400-group tumors. Moreover, mutation rates of immunoglobulin heavy chain sequences in the spleen within complementarity determining region 2 and framework region 3 were significantly higher in the mDX400 group than in the mIgG1 group. The findings of this study may contribute to an improved understanding of the molecular mechanisms of anti-Pd-1 treatment.

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T‐cell receptor and B‐cell receptor repertoire profiling in adaptive immunity

Cited by 55 publications

References 148 publications

Inferring the immune response from repertoire sequencing

Inferring the immune response from repertoire sequencing

<p>Toll-Like Receptor 9 Agonists in Cancer</p>

Comprehensive investigation of T and B cell receptor repertoires in an MC38 tumor model following murine anti‑PD‑1 administration

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