T Cell Receptor Clonotype Influences Epitope Hierarchy in the CD8+ T Cell Response to Respiratory Syncytial Virus Infection

Billam, P.; Bonaparte, Kathryn L.; Liu, Jie; Ruckwardt, Tracy J.; Chen, Man; Ryder, Alex B.; Wang, Rui; Dash, Pradyot; Thomas, Paul G.; Graham, Barney S.

doi:10.1074/jbc.m110.191437

Cited by 30 publications

(37 citation statements)

References 73 publications

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“…5F). While we were preparing the manuscript, similar results regarding the V␤ usage of epitope-specific CTL (using the different IMGT [international ImMunoGeneTics information system] nomenclature) in BALB/c and C57BL/6 mice were published by Graham and colleagues (3). Of note, the coexpression of the H-2 b allele, which protected from RSV-induced weight loss, led to a significant reduction in the dominant H-2 d -restricted CTL population and to a more diverse CTL response (Fig.…”

Section: Introduction Of the H-2mentioning

confidence: 74%

Major Histocompatibility Complex-Dependent Cytotoxic T Lymphocyte Repertoire and Functional Avidity Contribute to Strain-Specific Disease Susceptibility after Murine Respiratory Syncytial Virus Infection

Jessen

Faller

Krempl

et al. 2011

J Virol

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Section: Introduction Of the H-2mentioning

confidence: 74%

Major Histocompatibility Complex-Dependent Cytotoxic T Lymphocyte Repertoire and Functional Avidity Contribute to Strain-Specific Disease Susceptibility after Murine Respiratory Syncytial Virus Infection

Jessen

Faller

Krempl

et al. 2011

J Virol

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“…Public T cells are characterized by the expression of identical or highly related TCR Vα and/or Vβ genes that are present in the majority of subjects, dominate the response to a specific epitope, and dictate disease severity, despite being restricted in nature (26–33). Importantly, this type of TCR bias has been infrequently demonstrated in CD4 + T cells obtained from blood or the target organ of human subjects due in large part to unknown stimulatory antigens.…”

Section: Discussionmentioning

confidence: 99%

Shared αβ TCR Usage in Lungs of Sarcoidosis Patients with Löfgren’s Syndrome

Mitchell

Kaiser

Falta

et al. 2017

The Journal of Immunology

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Sarcoidosis is a granulomatous disease that primarily affects the lungs and is characterized by an accumulation of CD4+ T cells in the bronchoalveolar lavage (BAL). Previous work has indicated that HLA-DRB1*03:01+ (DR3+) patients diagnosed with the acute form of the disease, Löfgren’s syndrome (LS), have an accumulation of CD4+ T cells bearing TCRs utilizing TRAV12-1 (formerly AV2S3). However, the importance of these α-chains in disease pathogenesis and the paired TCRβ chain remains unknown. This study aimed to identify expanded αβTCR pairs expressed on CD4+ T cells derived from the BAL of DR3+ LS patients. Using a deep-sequencing approach, we determined the TCRα and TCRβ chain usage as well as αβTCR pairs expressed on BAL CD4+ T cells from LS patients. TRAV12-1 and TRBV2 (formerly BV22) were the most expanded V region gene segments in DR3+ LS patients relative to control subjects, and TRAV12-1 and TRBV2 CDR3 motifs were shared between multiple DR3+ LS patients. When assessing αβTCR pairing, TRAV12-1 preferentially paired with TRBV2, and these TRAV12-1/TRBV2 TCRs displayed CDR3 homology. These findings suggest that public CD4+ T cell receptor repertoires exist amongst Löfgren’s syndrome patients and that these T cells are recognizing the putative sarcoidosis-associated antigen(s) in the context of HLA-DR3.

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“…Increasing the number of clones sampled and subsequent analyses of those clones should enable broad coverage of the T-cell response. The ability to establish clonal lines also should allow additional characterization, such as the determination of clonotypes and proliferative capacity (39).…”

Section: Discussionmentioning

confidence: 99%

Rapid, efficient functional characterization and recovery of HIV-specific human CD8 ⁺ T cells using microengraving

Varadarajan

Kwon

Law

et al. 2012

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

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The nature of certain clinical samples (tissue biopsies, fluids) or the subjects themselves (pediatric subjects, neonates) often constrain the number of cells available to evaluate the breadth of functional T-cell responses to infections or therapeutic interventions. The methods most commonly used to assess this functional diversity ex vivo and to recover specific cells to expand in vitro usually require more than 10 6 cells. Here we present a process to identify antigen-specific responses efficiently ex vivo from 10 4 –10 5 single cells from blood or mucosal tissues using dense arrays of subnanoliter wells. The approach combines on-chip imaging cytometry with a technique for capturing secreted proteins—called “microengraving”—to enumerate antigen-specific responses by single T cells in a manner comparable to conventional assays such as ELISpot and intracellular cytokine staining. Unlike those assays, however, the individual cells identified can be recovered readily by micromanipulation for further characterization in vitro. Applying this method to assess HIV-specific T-cell responses demonstrates that it is possible to establish clonal CD8 + T-cell lines that represent the most abundant specificities present in circulation using 100- to 1,000-fold fewer cells than traditional approaches require and without extensive genotypic analysis a priori. This rapid (<24 h), efficient, and inexpensive process should improve the comparative study of human T-cell immunology across ages and anatomic compartments.

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T Cell Receptor Clonotype Influences Epitope Hierarchy in the CD8+ T Cell Response to Respiratory Syncytial Virus Infection

Cited by 30 publications

References 73 publications

Major Histocompatibility Complex-Dependent Cytotoxic T Lymphocyte Repertoire and Functional Avidity Contribute to Strain-Specific Disease Susceptibility after Murine Respiratory Syncytial Virus Infection

Major Histocompatibility Complex-Dependent Cytotoxic T Lymphocyte Repertoire and Functional Avidity Contribute to Strain-Specific Disease Susceptibility after Murine Respiratory Syncytial Virus Infection

Shared αβ TCR Usage in Lungs of Sarcoidosis Patients with Löfgren’s Syndrome

Rapid, efficient functional characterization and recovery of HIV-specific human CD8 ⁺ T cells using microengraving

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T Cell Receptor Clonotype Influences Epitope Hierarchy in the CD8+ T Cell Response to Respiratory Syncytial Virus Infection

Cited by 30 publications

References 73 publications

Major Histocompatibility Complex-Dependent Cytotoxic T Lymphocyte Repertoire and Functional Avidity Contribute to Strain-Specific Disease Susceptibility after Murine Respiratory Syncytial Virus Infection

Major Histocompatibility Complex-Dependent Cytotoxic T Lymphocyte Repertoire and Functional Avidity Contribute to Strain-Specific Disease Susceptibility after Murine Respiratory Syncytial Virus Infection

Shared αβ TCR Usage in Lungs of Sarcoidosis Patients with Löfgren’s Syndrome

Rapid, efficient functional characterization and recovery of HIV-specific human CD8 + T cells using microengraving

Contact Info

Product

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About

Rapid, efficient functional characterization and recovery of HIV-specific human CD8 ⁺ T cells using microengraving