Patient‐shared TCRβ‐CDR3 clonotypes correlate with favorable prognosis in chronic hepatitis B

Abstract

The presence of shared T-cell clonotypes was found in several different diseases, but its relationship with the progression of disease remains unclear. By sequencing the complementary determining region 3 of T-cell receptor (TCR) β chains from the purified antigen-experienced CD8 T cells, we characterized the T-cell repertoire in a prospective cohort study among 75 patients with chronic hepatitis B in China, as well as a healthy control and a validation cohort. We found that most T-cell clones from patients harbored the "patient-specific" TCR sequences. However, "patient-shared" TCR clonotypes were also widely found, which correlated with the favorable turnover of disease. Interestingly, the frequency of the "patient-shared" clonotypes can serve as a biomarker for favorable prognosis. Based on the clonotypes in those patients with favorable outcomes, we created a database including several clusters of protective anti-HBV CD8 T-cell clonotypes that might be a reasonable target for therapeutic vaccine development or adoptive cell transfer therapy. These findings were validated in an additional independent cohort of patients. These results suggest that the "patient-shared" TCR clonotypes may serve as a valuable prognostic tool in the treatment of chronic hepatitis B and possibly other chronic viral diseases.

A scoring system for the electrostatic complementarities of T‐cell receptors and cancer‐mutant amino acids: multi‐cancer analyses of associated survival rates

“…More recently, several additional tools that have the potential of contributing to a resolution of some of the above issues have become available. First, bioinformatics and computational approaches have made it clear that chemical and structural features of the TCR complementarity‐determining region 3 (CDR3) can correlate with a specific immune response . This development points to the second development, the employment of which offers promise for learning more about specific cancer patient, TCR CDR3, mutant peptide interactions, namely the vast databases now available representing cancer patient mutant amino acids (aa) and tens of thousands of TCR CDR3s for the corresponding TILs.…”

Partial recovery of disturbed V-J pairing profiles of T-cell receptor in people living with HIV receiving long-term antiretroviral therapy

“…Specificity describes the subtle details of T cell clones, whereas diversity provides a more general view of the entire T cell population. In most studies on the TCR repertoire, high-throughput sequencing of the CDR3 coding region has successfully described the specificity of TCR for recognizing specific peptides of pathogens, tumour cells and auto-antigens (Billam et al, 2011;Farge et al, 2017;Jiang et al, 2018;McNeel, 2016;Miyasaka et al, 2019;Ochsenreither et al, 2012;Zhao et al, 2016). Unlike the diseases related to mono-or oligo-clonal changes of T cells, the disturbance of CD4 + T cells caused by HIV infection is severe and broad (Baum et al, 2012).…”

“…The generation of TCR diversity occurs in the precursor T cells in the thymus by the random and imprecise somatic rearrangement of segregated germline variable (V) and joining (J) gene segments for the TCR α chain and segregated germline V, diversity (D) and J gene segments for the TCR β chain (Call et al, 2006;Mallis et al, 2015;McDonald et al, 2015). Since the hypervariable complementarity determining region 3 (CDR3) of TCRs determines the antigenic specificity of one given T cell (Call et al, 2004;Dash et al, 2017;Glanville et al, 2017), the sequences coding CDR3 have been extensively studied in the fields focusing on TCR specificity, such as anti-tumour immunity, vaccine development, and autoimmune diseases (Billam et al, 2011;Farge et al, 2017;Jiang et al, 2018;McNeel, 2016;Miyasaka et al, 2019;Ochsenreither et al, 2012;Zhao et al, 2016).…”

High throughput sequencing of T-cell receptor repertoire using dry blood spots

“…Even for infection disease, TCR repertoire was explored the function profile of T cells in HIV patients and the characteristics of immune landscape after injection of HIV vaccine [6, 39]. TCRβ-CDR3 were correlated with disease prognosis of hepatitis B and C [5, 40, 41]. DBS-based methodology provides a simple and quick approach to access changes of immunity and treatment effect in different disease areas.…”