# T Cell Repertoire Analysis as a Molecular Signature of the Spectrum of T-LGL Lymphoproliferative Disorders: Tracing the Literature

## TL;DR

This review explores how T cell repertoire patterns help understand the progression of T-LGL lymphoproliferative disorders from normal to malignant states.

## Contribution

The paper synthesizes findings on T cell receptor repertoire dynamics to propose shared antigen-driven mechanisms in T-LGL disorders.

## Key findings

- T-LGL disorders show skewed TRBV repertoires and multiple immunodominant clonotypes.
- Persistent clonotypes with fluctuating frequencies (clonal drift) are observed over time.
- Shared public clonotypes suggest limited antigens are involved in T-LGL pathogenesis.

## Abstract

CD3+ CD8+ CD57+ mono-, oligo-, and poly-clonal expansions, both idiopathic and clinically related diseases, including as autoimmunity, viral infections, post-transplant, and hematologic malignancies, can cause T large granular lymphocyte (T-LGL) lymphoproliferative disorders. It is yet unknown if this variability is a result of a dynamic process of cytotoxic T cell responses to exoantigens and autoantigens. The major aim of this review is to gather evidence from the literature in order to further highlight the possible pathogenetic mechanism that may underly the above clinical entities. Major research findings include the following: (i) pronounced skewing of the TRBV repertoire; (ii) existence of more than one immunodominant clonotype; (iii) persistent clonotypes in different timepoints albeit with fluctuating frequencies (clonal drift); and (iv) shared (‘public’) clonotypes between cases and the public databases, further suggesting a limited number of antigens implicated in pathogenesis of T-LGL cases. However, there is no clear distinction between polyclonal, oligoclonal, and monoclonal T-LGL lymphoproliferative conditions; rather, the progression from a polyclonal cytotoxic response to the emergence of T-LGL leukemia is slow. In the ontogeny and evolution of T-LGL leukemia, repertoire limits, public clonotypes, and clonal drift all clearly show selection by limited (perhaps shared) antigens.