Epstein Barr virus epitope/MHC interaction combined with convergent recombination drive selection of diverse T cell receptor α and β repertoires

Gil, Anna; Kamga, Larisa; Chirravuri-Venkata, Ramakanth; Aslan, Nuray; Clark, Fransenio G.; Ghersi, Dario; Luzuriaga, Katherine; Selin, Liisa K.

doi:10.1101/2020.02.06.938241

Cited by 2 publications

(1 citation statement)

References 78 publications

(104 reference statements)

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“…The frequency of BV19 usage increased in donor D002 in EBV-BM and EBV-BR specific TRBV repertoires, despite it having been established as a public response to IAV-M1, while it decreased in the IAV-M1 response (Figure 6). Furthermore, in D002 the IAV-M1 response had dominant usage of BV2, BV29, BV27 and BV20 (72) all public BV for EBV-BM responses, while the dramatically increased usage of BV5.1 and BV6.6 are BV that are usually associated with EBV-BR responses (72). The TRBV repertoire for EBV-BM specific responses maintained a dominant use of TRBV14 for both donors until acute IAV infection, during which BV20 usage increased in both EBV-BM and -BR specific responses, as well as IAV-M1 responses (Figure 6,7).…”

Section: Trbv Repertoire To Iav-m1 Ebv-bm and Ebv-br Are Continuously...mentioning

confidence: 99%

Co-evolution of human influenza A and Epstein Barr virus-specific CD8 ex vivo memory T cell receptor BV repertoires with increasing age

Clark

Gil

Aslan

et al. 2022

Preprint

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CD8 memory T cells are generated during primary infection with intracellular pathogens, such as viruses. These cells play an important role in the protection of the host upon re-infection with the same pathogen. In this study, we compare CD8 memory T cell receptor (TCR) beta repertoires directly ex vivo for two common human viruses, influenza A virus (IAV), an RNA virus that frequently re-infects due to a high rate of genetic mutation, and Epstein-Barr virus (EBV), a DNA virus, which persists in B cells for life, in the 95% of people that become infected. In cross-sectional and longitudinal studies of EBV seropositive, HLA-A2+, young (18-22 years), middle age (25-59 years), and older (>60 years) donors, we demonstrate that CD8 memory TCR repertoires to three immunodominant epitopes, known to have cross-reactive responses, IAV-M158-66 (M1), EBV-BMLF1280-288 (BM), and EBV-BRLF109-117 (BR) co-evolve as individuals age. Cross-sectional studies showed that IAV-M1- and both EBV-specific repertoires narrowed their TRBV usage with increasing age manifesting to different degrees for each epitope. In fact, narrowing of EBV-BM and EBV-BR-specific TRBV family usage correlated with increasing age. IAV-M1-specific TRBV usage was significantly narrowed by middle-age. There was evidence that TRBV usage was changing with increasing age. For instance, IAV-M1-specific dominant BV19 usage appeared to become bimodal showing either high or low frequency of usage in the older age group, while BV30 usage frequency directly correlated with age. For the EBV epitope-specific responses there was preferential usage of particular TRBV and changes in the hierarchy of BV family usage in the different age groups. There appeared to be focusing of the TRBV repertoire by all 3 epitopes to three common BV in the older donors, which would be consistent with retention of cross-reactive TCR suggesting co-evolution. Longitudinal studies tracking two donors over 14-15 years (middle age to older) showed that there were continuous modulations in the TCR repertoire of IAV-M1, EBV-BM and EBV-BR-specific responses over time. There was evidence that acute IAV infection could contribute to these changes in TCR repertoire. This could be occurring by the TCR cross-reactivity that is known to exist between these 3 epitopes, and which appeared to be enhanced during acute IAV infection based on increased usage of common shared TRBV. These studies suggest that virus-specific TCR repertoires change over time as individuals age leading to narrowing of the repertoire favoring retention of potentially cross-reactive TCR.

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Section: Trbv Repertoire To Iav-m1 Ebv-bm and Ebv-br Are Continuously...mentioning

confidence: 99%

Co-evolution of human influenza A and Epstein Barr virus-specific CD8 ex vivo memory T cell receptor BV repertoires with increasing age

Clark

Gil

Aslan

et al. 2022

Preprint

Self Cite

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Quantitative Annotations of T-Cell Repertoire Specificity

Luo

Zou

Chen

et al. 2023

Preprint

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The specificity of a T-cell receptor (TCR) repertoire determines personalized immune capacity. Existing methods have modelled the qualitative aspects of TCR specificity, while the quantitative aspects remained unaddressed. We developed a package, TCRanno, to quantify the specificity of TCR repertoires. Applying TCRanno to 4,195 TCR repertoires revealed quantitative changes in repertoire specificity upon infections, autoimmunity and cancers. Specifically, TCRanno found cytomegalovirus-specific TCRs in seronegative healthy individuals, indicating their past abortive infections instead of non-exposure to the virus. TCRanno discovered age-accumulated SARS-CoV2 specific TCRs in pre-pandemic samples, which may explain the aggressive symptoms and age-related severity of COVID-19. TCRanno also identified the encounter of Hepatitis B antigens as a trigger of systemic lupus erythematosus. TCRanno annotations showed capability in distinguishing TCR repertoires of healthy and cancers including melanoma, lung and breast cancers. TCRanno also demonstrated usefulness to single-cell TCRseq+gene expression data analyses by isolating T-cells with the specificity of interest.

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Epstein Barr virus epitope/MHC interaction combined with convergent recombination drive selection of diverse T cell receptor α and β repertoires

Abstract: Epstein Barr virus epitope/MHC interaction combined with convergent 1recombination drive selection of diverse T cell receptor and repertoires 2 3 4

Cited by 2 publications

References 78 publications

Co-evolution of human influenza A and Epstein Barr virus-specific CD8 ex vivo memory T cell receptor BV repertoires with increasing age

Co-evolution of human influenza A and Epstein Barr virus-specific CD8 ex vivo memory T cell receptor BV repertoires with increasing age

Quantitative Annotations of T-Cell Repertoire Specificity

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