Limited T Cell Receptor Repertoire Diversity in Tuberculosis Patients Correlates with Clinical Severity

Luo, Wei; Su, Jin; Zhang, Xiaobing; Liu, Yang; Zhou, Meijun; Jiang, Zhen-Min; Hao, Pei-Pei; Liu, Sudong; Wen, Qian; Jin, Qi; Ma, Li

doi:10.1371/journal.pone.0048117

Cited by 38 publications

(27 citation statements)

References 30 publications

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“…Luo et al (54) screened TCR Vα11 and Vβ8 expression in CD4 + T cells and TCR Vα3 and Vβ8 expression in CD8 + T cells because these are specific for a 38-kDa antigen of M. tuberculosis; following transduction into primary CD4 + and CD8 + T cells, these specific genes induced anti-M. tuberculosis activity. Furthermore, the CDR3 spectratypes of two T cell subpopulations were also analysed in 86 patients with different degrees of TB (55), and patients with TB were found to possess a restricted TCR repertoire when compared with healthy controls. A sequence analysis of CDR3 in clonally expanded T cells revealed a highly conserved amino acid motif in both the TCR α and β chains.…”

Section: Tuberculosis Tuberculosis (Tb) Which Is Caused Bymentioning

confidence: 99%

αβ T-cell receptor bias in disease and therapy (Review)

Wang

et al. 2016

International Journal of Oncology

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Abstract.The diversity and specificity of T cell receptors (TCR), the characteristics of T-cell surface marker, are central to the adaptive immunity. TCR variability is required for successful immunization coverage because this structural foundation is indispensable for the valid identification of short antigen peptides (derived from degraded antigens) that are presented by major histocompatibility molecules on the surfaces of antigen-presenting cells. Despite the vast T-cell repertoire, biased αβ TCR has become a common theme in immunology. To date, numerous examples of TCR bias have been observed in various diseases. Immunotherapy strategies that are based on αβ T cell responses are also emerged as a prominent component of clinical treatment. In the present review, we briefly summarize the current knowledge regarding basic structural information and the molecular mechanisms underlying TCR diversity. Moreover, we outline the role of TCR repertoire bias in some diseases, and its application for therapeutic interventions, as these play significant roles in disease progression, even with patients with a good prognosis.

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Section: Tuberculosis Tuberculosis (Tb) Which Is Caused Bymentioning

confidence: 99%

αβ T-cell receptor bias in disease and therapy (Review)

Wang

et al. 2016

International Journal of Oncology

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“…Spectratyping of peripheral blood CD4+ and CD8+ T cells from pediatric and adult tuberculosis patients found skewing of the TCR repertoires compared to healthy controls [62-64]. Extreme TCR bias (e.g., clonality) was noted primarily in the setting of severe clinical disease, raising the possibility that TCR bias is associated with disease progression [62,65]. Arguing against this interpretation is the presence of highly skewed TCR repertoires in lung granulomas from patients with latent tuberculosis, with as many as 27% of CD4s and 17% of CD8s being clonal [66].…”

Section: Integration Of Multiple Signals During T Cell Priming Detmentioning

confidence: 99%

Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: Immunity interruptus

Behar¹,

Carpenter²,

Booty³

et al. 2014

Seminars in Immunology

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Despite the introduction almost a century ago of Mycobacterium bovis BCG (BCG), an attenuated form of M. bovis that is used as a vaccine against Mycobacterium tuberculosis, tuberculosis remains a global health threat and kills more than 1.5 million people each year. This is mostly because BCG fails to prevent pulmonary disease – the contagious form of tuberculosis. Although there have been significant advances in understanding how the immune system responds to infection, the qualities that define protective immunity against M. tuberculosis remain poorly characterized. The ability to predict who will maintain control over the infection and who will succumb to clinical disease would revolutionize our approach to surveillance, control, and treatment. Here we review the current understanding of pulmonary T cell responses following M. tuberculosis infection. While infection elicits a strong immune response that contains infection, M. tuberculosis evades eradication. Traditionally, its intracellular lifestyle and alteration of macrophage function are viewed as the dominant mechanisms of evasion. Now we appreciate that chronic inflammation leads to T cell dysfunction. While this may arise as the host balances the goals of bacterial sterilization and avoidance of tissue damage, it is becoming clear that T cell dysfunction impairs host resistance. Defining the mechanisms that lead to T cell dysfunction is crucial as memory T cell responses are likely to be subject to the same subject to the same pressures. Thus, success of T cell based vaccines is predicated on memory T cells avoiding exhaustion while at the same time not promoting overt tissue damage.

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“…Moreover, different mechanisms of memory recruitment have different long-term implications for the clonal diversity of epitope-specific populations, especially with repeated virus exposure. Repeated selection of particular clones inherent in deterministic clonal selection has the potential consequence of narrowing the CTL repertoire, whereas stochastic recruitment/expansion seems more likely to maintain CTL diversity, shown to be beneficial for virus control (3)(4)(5)(6)(7). Despite the implications, there remains conjecture about how epitope-specific CD8 + T cells are recruited from the memory pool.…”

Section: Recall Cd8mentioning

confidence: 99%

Reproducible selection of high avidity CD8 ⁺ T-cell clones following secondary acute virus infection

Cukalac

Chadderton

Handel³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The recall of memory CD8 + cytotoxic T lymphocytes (CTLs), elicited by prior virus infection or vaccination, is critical for immune protection. The extent to which this arises as a consequence of stochastic clonal expansion vs. active selection of particular clones remains unclear. Using a parallel adoptive transfer protocol in combination with single cell analysis to define the complementarity determining region (CDR) 3α and CDR3β regions of individual Tcell receptor (TCR) heterodimers, we characterized the antigendriven recall of the same memory CTL population in three individual recipients. This high-resolution analysis showed reproducible enrichment (or diminution) of particular TCR clonotypes across all challenged animals. These changes in clonal composition were TCRα− and β chain-dependent and were directly related to the avidity of the TCR for the virus-derived peptide (p) + major histocompatibility complex class I molecule. Despite this shift in clonotype representation indicative of differential selection, there was no evidence of overall repertoire narrowing, suggesting a strategy to optimize CTL responses while safeguarding TCR diversity.+ cytotoxic T lymphocytes (CTLs) are key for effective pathogen clearance. To exert their antiviral effects, naïve CD8 + CTL precursors (CTLps) must first be activated through the specific recognition of virus-derived peptides (p) in the context of major histocompatibility complex class I molecules (MHCI) expressed on the surface of dendritic cells. Ligation of these pMHCI epitopes is mediated via specific T-cell receptor (TCR) αβ heterodimers, leading to the recruitment, proliferation, and activation of antigen-specific CTLs. Subsequent to virus clearance, CTL populations contract to form a stable pool of resting memory cells, typically at around 5-10% of their acute phase numbers (1, 2). On secondary virus encounter, this memory pool of CD8 + T cells is able to expand rapidly, providing potent immune protection (2).An understanding of CD8 + T-cell recruitment/expansion into the recall response has significant implications for effective vaccine strategies. If recruitment and expansion occur stochastically, a memory population in which highly effective clones predominate is desirable. Alternatively, if selection is deterministic, the basic requirement would be the presence of highquality clones in the memory population for selective expansion by antigen-driven mechanisms. Moreover, different mechanisms of memory recruitment have different long-term implications for the clonal diversity of epitope-specific populations, especially with repeated virus exposure. Repeated selection of particular clones inherent in deterministic clonal selection has the potential consequence of narrowing the CTL repertoire, whereas stochastic recruitment/expansion seems more likely to maintain CTL diversity, shown to be beneficial for virus control (3-7). Despite the implications, there remains conjecture about how epitope-specific CD8 + T cells are recruited from the memory pool. Studies h...

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Limited T Cell Receptor Repertoire Diversity in Tuberculosis Patients Correlates with Clinical Severity

Cited by 38 publications

References 30 publications

αβ T-cell receptor bias in disease and therapy (Review)

αβ T-cell receptor bias in disease and therapy (Review)

Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: Immunity interruptus

Reproducible selection of high avidity CD8 ⁺ T-cell clones following secondary acute virus infection

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Limited T Cell Receptor Repertoire Diversity in Tuberculosis Patients Correlates with Clinical Severity

Cited by 38 publications

References 30 publications

αβ T-cell receptor bias in disease and therapy (Review)

αβ T-cell receptor bias in disease and therapy (Review)

Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: Immunity interruptus

Reproducible selection of high avidity CD8 + T-cell clones following secondary acute virus infection

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Reproducible selection of high avidity CD8 ⁺ T-cell clones following secondary acute virus infection