Background: Several B-cell malignancies present evidence of stereotyped B-cell receptors and antigen driven pathogenesis. By contrast, this phenomenon has not been documented in T-cell lymphomas (TCL), an heterogeneous group of aggressive malignancies.
Objective: This study aims to assess the occurrence of stereotyped TRG rearrangements in TCL and explore their potential association with exogenous antigens.
Methods: 109 tissue samples were collected at the IRCCS Azienda Ospedaliera-Universitaria di Bologna, Policlinico di S. Orsola. DNA from lymph node tissues was extracted and analyzed using PCR-based and next-generation sequencing (NGS) methods to identify TRG gene rearrangements. Sequence analysis was carried out to identify possibly recurrent rearrangements (i.e. stereotypes). Stereotyped sequences were then translated into proteins, and potential interactions with bacterial antigens were assessed using bioinformatics tools, including BLAST and AlphaFold.
Results: Out of 109 cases, 54 (49.54%) cases, corresponding to T-cell lymphomas, were identified as monoclonal. Sequences analyses revealed a higher prevalence of certain TRG families, suggesting the presence of stereotyped rearrangements. Further studies identified potential interactions between some TRG and bacterial proteins, including Legionella jordanis, indicating a possible antigen-driven mechanism in TCL pathogenesis.
Conclusion: The identification of stereotyped TRG rearrangements supports the hypothesis of an antigen-driven process in TCL, with bacterial proteins potentially playing a role in lymphoma development. These findings provide a novel insights into the mechanisms of lymphomagenesis and may contribute to the improvement of TCL prevention and early recognition. Further studies are needed to validate these associations and elucidate their clinical significance.
