Utility of Bulk T-Cell Receptor Repertoire Sequencing Analysis in Understanding Immune Responses to COVID-19
Abstract
:1. Introduction
2. Overview of T-Cells in COVID-19
2.1. Immunological Memory and Longevity
2.2. T-Cell Cross-Reactivity
2.3. Pathogenic Effects of T Cells
2.4. T-Cell Tests in Current Clinical Use
3. The TCR Repertoire
3.1. Sample Cohort Building for TCR Repertoire Analysis
3.2. Laboratory Methods in ‘Bulk’ TCR Repertoire Sequencing
3.2.1. Substrate for Repertoire Sequencing
3.2.2. Methodological Considerations
3.3. Analysis of “Bulk” TCR Repertoire Sequencing
3.3.1. Principles of Analysis of CDR3 Sequences
3.3.2. Clonotypic Analysis
3.3.3. Diversity Profiling and Related Analyses
Analytical Approach | Principles/Interpretation |
---|---|
CDR3 length profiles [59] |
|
VDJ usage |
|
Clonal abundance |
|
Clonal frequency |
|
Richness [62] |
|
D50 diversity [64] |
|
Simpson diversity [65,66,67] |
|
Shannon diversity [61,67,69,70,71] |
|
Hill’s diversity (Hill’s evenness) [73] |
|
Pielou’s evenness index [64] |
|
Parametric methods [74] |
|
3.3.4. Analyses Based on Sequence or Motif Identification
3.3.5. Machine Learning to Predict Diagnosis, Exposure to Infection or Outcome of Infection
3.3.6. Machine Learning to Identify New Antigen-Specific Sequences
4. Biological Insights into COVID-19 from T-Cell Receptor Analysis
4.1. Relative Contributions of T Cells and B Cells to SARS-CoV-2 Immunity
4.2. Association between Higher Repertoire Diversity and Improved Outcomes
4.3. Kinetics of CD4 and CD8 T-Cell Responses
4.4. Importance of Specific V-, D- and J-Segment Usage
4.5. Importance of SARS-CoV-2 Specific TCR Sequences and Motifs
First Author | Number of Samples | Cells | DNA/RNA | Loci | Key Points |
---|---|---|---|---|---|
Chang [97] |
| PBMCs | RNA | TRB |
|
Cheng [5] |
| PBMCs | DNA | TRB |
|
Minervina [99] |
| CD4+ and CD8+ T cells | RNA | TRB TRA |
|
Niu [96] |
| PBMCs | RNA | TRB TRA TRG TRD |
|
Rajeh [89] |
| PBMCs | RNA | TRB TRA |
|
Schultheiss [95] |
| PBMCs | DNA | TRB |
|
Shomuradova [94] |
| CD4+ and CD8+ T cells | RNA | TRB TRA |
|
Shoukat [14] |
| PBMCs | DNA | TRB |
|
Sidhom [92] |
| PBMCs | DNA | TRB |
|
Swanson [99] |
| PBMCs | DNA | TRB |
|
Wang [100] |
| CD4+ and CD8+ T cells | RNA | TRB TRA |
|
Hu [101] |
| PBMCs | RNA | TRB |
|
Simnica [102] |
| PBMCs Brain-derived T cells; | DNA | TRB |
|
Shimizu [103] |
| CD8+ T cells | DNA | TRB TRA |
|
Li [104] |
| PBMCs | RNA | TRB |
|
4.6. Vaccine-Induced T-Cell Responses in Comparison to Responses to Native Infection
5. Areas for Further Research
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Method | DNA/RNA | Principles | Advantages | Disadvantages | Examples of Manufacturers |
---|---|---|---|---|---|
5′RACE | RNA |
|
|
| iRepertoire, Clontech/Takara, MiLaboratories |
Multiplex PCR | DNA, RNA |
|
|
| Adaptive Biotechnologies (Immunoseq); Invivoscribe (Lymphotrack) |
Hybridisation capture | DNA, RNA |
|
|
| Bespoke approaches |
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Kockelbergh, H.; Evans, S.; Deng, T.; Clyne, E.; Kyriakidou, A.; Economou, A.; Luu Hoang, K.N.; Woodmansey, S.; Foers, A.; Fowler, A.; et al. Utility of Bulk T-Cell Receptor Repertoire Sequencing Analysis in Understanding Immune Responses to COVID-19. Diagnostics 2022, 12, 1222. https://doi.org/10.3390/diagnostics12051222
Kockelbergh H, Evans S, Deng T, Clyne E, Kyriakidou A, Economou A, Luu Hoang KN, Woodmansey S, Foers A, Fowler A, et al. Utility of Bulk T-Cell Receptor Repertoire Sequencing Analysis in Understanding Immune Responses to COVID-19. Diagnostics. 2022; 12(5):1222. https://doi.org/10.3390/diagnostics12051222
Chicago/Turabian StyleKockelbergh, Hannah, Shelley Evans, Tong Deng, Ella Clyne, Anna Kyriakidou, Andreas Economou, Kim Ngan Luu Hoang, Stephen Woodmansey, Andrew Foers, Anna Fowler, and et al. 2022. "Utility of Bulk T-Cell Receptor Repertoire Sequencing Analysis in Understanding Immune Responses to COVID-19" Diagnostics 12, no. 5: 1222. https://doi.org/10.3390/diagnostics12051222