tetano
Editor, Senior Moderator
Hum Genomics
. 2024 Sep 4;18(1):94.
doi: 10.1186/s40246-024-00654-0. The T-cell repertoire of Spanish patients with COVID-19 as a strategy to link T-cell characteristics to the severity of the disease
Fernando Marín-Benesiu[SUP] #[/SUP][SUP] 1 2 [/SUP], Lucia Chica-Redecillas[SUP] #[/SUP][SUP] 1 2 [/SUP], Verónica Arenas-Rodríguez[SUP] 2 [/SUP], Esperanza de Santiago[SUP] 2 [/SUP], Silvia Martínez-Diz[SUP] 3 [/SUP], Ginesa López-Torres[SUP] 4 [/SUP], Ana Isabel Cortés-Valverde[SUP] 4 [/SUP], Catalina Romero-Cachinero[SUP] 5 [/SUP], Carmen Entrala-Bernal[SUP] 6 [/SUP], Francisco Javier Fernandez-Rosado[SUP] 6 [/SUP], Luis Javier Martínez-González[SUP] #[/SUP][SUP] 7 8 [/SUP], Maria Jesus Alvarez-Cubero[SUP] #[/SUP][SUP] 1 2 9 [/SUP]
Affiliations
Background: The architecture and dynamics of T cell populations are critical in orchestrating the immune response to SARS-CoV-2. In our study, we used T Cell Receptor sequencing (TCRseq) to investigate TCR repertoires in 173 post-infection COVID-19 patients.
Methods: The cohort included 98 mild and 75 severe cases with a median age of 53. We amplified and sequenced the TCR β chain Complementary Determining Region 3 (CDR3b) and performed bioinformatic analyses to assess repertoire diversity, clonality, and V/J allelic usage between age, sex and severity groups. CDR3b amino acid sequence inference was performed by clustering structural motifs and filtering validated reactive CDR3b to COVID-19.
Results: Our results revealed a pronounced decrease in diversity and an increase in clonal expansion in the TCR repertoires of severe COVID-19 patients younger than 55 years old. These results reflect the observed trends in patients older than 55 years old (both mild and severe). In addition, we identified a significant reduction in the usage of key V alleles (TRBV14, TRBV19, TRBV15 and TRBV6-4) associated with disease severity. Notably, severe patients under 55 years old had allelic patterns that resemble those over 55 years old, accompanied by a skewed frequency of COVID-19-related motifs.
Conclusions: Present results suggest that severe patients younger than 55 may have a compromised TCR repertoire contributing to a worse disease outcome.
Keywords: Adaptative immunology; COVID-19; Immunoinformatics; SARS-Cov2; T cells; TCR repertoire.
. 2024 Sep 4;18(1):94.
doi: 10.1186/s40246-024-00654-0. The T-cell repertoire of Spanish patients with COVID-19 as a strategy to link T-cell characteristics to the severity of the disease
Fernando Marín-Benesiu[SUP] #[/SUP][SUP] 1 2 [/SUP], Lucia Chica-Redecillas[SUP] #[/SUP][SUP] 1 2 [/SUP], Verónica Arenas-Rodríguez[SUP] 2 [/SUP], Esperanza de Santiago[SUP] 2 [/SUP], Silvia Martínez-Diz[SUP] 3 [/SUP], Ginesa López-Torres[SUP] 4 [/SUP], Ana Isabel Cortés-Valverde[SUP] 4 [/SUP], Catalina Romero-Cachinero[SUP] 5 [/SUP], Carmen Entrala-Bernal[SUP] 6 [/SUP], Francisco Javier Fernandez-Rosado[SUP] 6 [/SUP], Luis Javier Martínez-González[SUP] #[/SUP][SUP] 7 8 [/SUP], Maria Jesus Alvarez-Cubero[SUP] #[/SUP][SUP] 1 2 9 [/SUP]
Affiliations
- PMID: 39227859
- PMCID: PMC11373388
- DOI: 10.1186/s40246-024-00654-0
Background: The architecture and dynamics of T cell populations are critical in orchestrating the immune response to SARS-CoV-2. In our study, we used T Cell Receptor sequencing (TCRseq) to investigate TCR repertoires in 173 post-infection COVID-19 patients.
Methods: The cohort included 98 mild and 75 severe cases with a median age of 53. We amplified and sequenced the TCR β chain Complementary Determining Region 3 (CDR3b) and performed bioinformatic analyses to assess repertoire diversity, clonality, and V/J allelic usage between age, sex and severity groups. CDR3b amino acid sequence inference was performed by clustering structural motifs and filtering validated reactive CDR3b to COVID-19.
Results: Our results revealed a pronounced decrease in diversity and an increase in clonal expansion in the TCR repertoires of severe COVID-19 patients younger than 55 years old. These results reflect the observed trends in patients older than 55 years old (both mild and severe). In addition, we identified a significant reduction in the usage of key V alleles (TRBV14, TRBV19, TRBV15 and TRBV6-4) associated with disease severity. Notably, severe patients under 55 years old had allelic patterns that resemble those over 55 years old, accompanied by a skewed frequency of COVID-19-related motifs.
Conclusions: Present results suggest that severe patients younger than 55 may have a compromised TCR repertoire contributing to a worse disease outcome.
Keywords: Adaptative immunology; COVID-19; Immunoinformatics; SARS-Cov2; T cells; TCR repertoire.