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Paired TCR?? analysis of virus-specific CD8(+) T cells exposes diversity in a previously defined 'narrow' repertoire.

ABSTRACT: T-cell receptor (TCR) usage has an important role in determining the outcome of CD8(+) cytotoxic T-lymphocyte responses to viruses and other pathogens. However, the characterization of TCR usage from which such conclusions are drawn is based on exclusive analysis of either the TCR? chain or, more commonly, the TCR? chain. Here, we have used a multiplexed reverse transcription-PCR protocol to analyse the CDR3 regions of both TCR? and ? chains from single naive or immune epitope-specific cells to provide a comprehensive picture of epitope-specific TCR usage and selection into the immune response. Analysis of TCR repertoires specific for three influenza-derived epitopes (D(b)NP(366), D(b)PA(224) and D(b)PB1-F2(62)) showed preferential usage of particular TCR?? proteins in the immune repertoire relative to the naive repertoire, in some cases, resulting in a complete shift in TRBV preference or CDR3 length, and restricted repertoire diversity. The NP(366)-specific TCR?? repertoire, previously defined as clonally restricted based on TCR? analysis, was similarly diverse as the PA(224)- and PB1-F2(62)-specific repertoires. Intriguingly, preferred TCR characteristics (variable gene usage, CDR3 length and junctional gene usage) appeared to be able to confer specificity either independently or in concert with one another, depending on the epitope specificity. These data have implications for established correlations between the nature of the TCR repertoire and response outcomes after infection, and suggest that analysis of a subset of cells or a single TCR chain does not accurately depict the nature of the antigen-specific TCR?? repertoire.

SUBMITTER: Cukalac T

PROVIDER: S-EPMC4618100 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Paired TCRαβ analysis of virus-specific CD8(+) T cells exposes diversity in a previously defined 'narrow' repertoire.

Cukalac Tania T Kan Wan-Ting WT Dash Pradyot P Guan Jing J Quinn Kylie M KM Gras Stephanie S Thomas Paul G PG La Gruta Nicole L NL

Immunology and cell biology 20150325 9

T-cell receptor (TCR) usage has an important role in determining the outcome of CD8(+) cytotoxic T-lymphocyte responses to viruses and other pathogens. However, the characterization of TCR usage from which such conclusions are drawn is based on exclusive analysis of either the TCRα chain or, more commonly, the TCRβ chain. Here, we have used a multiplexed reverse transcription-PCR protocol to analyse the CDR3 regions of both TCRα and β chains from single naive or immune epitope-specific cells to ...[more]

PMID: 25804828

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Project description:Thermal acclimation is hypothesized to offer a selective advantage in seasonal habitats and may underlie disparities in geographic range size among closely-related species with similar ecologies. Understanding this relationship is also critical for identifying species that are more sensitive to warming climates. Here, we study North American plethodontid salamanders to investigate whether acclimation ability is associated with species' latitudinal extents and the thermal range of the environments they inhabit. We quantified variation in thermal physiology by measuring standard metabolic rate (SMR) at different test and acclimation temperatures for 16 species of salamanders with varying latitudinal extents. A phylogenetically-controlled Markov chain Monte Carlo generalized linear mixed model (MCMCglmm) was then employed to determine whether there are differences in SMR between wide- and narrow-ranging species at different acclimation temperatures. In addition, we tested for a relationship between the acclimation ability of species and the environmental temperature ranges they inhabit. Further, we investigated if there is a trade-off between critical thermal maximum (CTMax) and thermal acclimation ability. MCMCglmm results show a significant difference in acclimation ability between wide and narrow-ranging temperate salamanders. Salamanders with wide latitudinal distributions maintain or slightly increase SMR when subjected to higher test and acclimation temperatures, whereas several narrow-ranging species show significant metabolic depression. We also found significant, positive relationships between acclimation ability and environmental thermal range, and between acclimation ability and CTMax. Wide-ranging salamander species exhibit a greater capacity for thermal acclimation than narrow-ranging species, suggesting that selection for acclimation ability may have been a key factor enabling geographic expansion into areas with greater thermal variability. Further, given that narrow-ranging salamanders are found to have both poor acclimation ability and lower tolerance to warm temperatures, they are likely to be more susceptible to environmental warming associated with anthropogenic climate change.

Dataset Information

Paired TCR?? analysis of virus-specific CD8(+) T cells exposes diversity in a previously defined 'narrow' repertoire.

Publications

Paired TCRαβ analysis of virus-specific CD8(+) T cells exposes diversity in a previously defined 'narrow' repertoire.

Similar Datasets

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