TCR repertoire dynamics and their responses underscores dengue severity

Despite recognizing the immune response’s role in dengue progression, the intricate dynamics of T cell receptor (TCR) variations across DENV infection severities remain elusive. This study addresses this gap by analyzing in-house generated RNA-seq data from 112 dengue patients with varying disease severities. Our findings reveal that severe dengue patients exhibit pronounced clinical manifestations including leukopenia, thrombocytopenia, and elevated lymphocyte levels, Intriguingly, these patients also showed increased diversity in γ and δ TCR chains, unique TRGV and TRBV segment usage, and extended δ-CDR3 sequences, suggesting specialized inflammatory functions. Furthermore, mutations in the NS5 and 3′UTR regions of the dengue genome correlated with increased TRDV and TRGV chains, indicating a significant role for these mutations in the prevalence of specific TCR chains during severe infections. Overall, the study highlights the complex role of TCR repertoire in dengue pathogenesis, enhancing our understanding of TCR dynamics for future infectious diseases. [Display omitted] •Elevated γδ TCR chains in severe dengue suggest key roles in inflammation•Severe dengue exhibits unique TRGV/TRBV usage and extended δ-CDR3 sequences•NS5 and 3′UTR mutations correlate with increased TRDV/TRGV chain abundance•TCR diversity and segment usage are linked to dengue severity and immune response Disease; Genomics; Virology