Analysis of peripheral blood TCRβ CDR3 repertoire characteristics in patients with multidrug-resistant tuberculosis

This exploratory study aimed to characterize peripheral blood TCRβ CDR3 repertoire features in patients with multidrug-resistant tuberculosis (MDR-TB) compared with drug-sensitive tuberculosis (DS-TB). TCRβ CDR3 diversity and clonotype composition were analyzed in five MDR-TB patients and five DS-TB patients using adaptive immune receptor repertoire sequencing (AIRR-seq). In this small exploratory cohort, MDR-TB patients showed lower overall clonotype numbers, increased dominant clone expansion, and a more focused T-cell response pattern. Seven recurrent CDR3 core motifs were detected in MDR-TB samples; however, because several motifs were short and lacked canonical IMGT-defined full-length CDR3 boundaries, these findings should be interpreted as candidate sequence features rather than validated antigen-specific TCR clonotypes. TCRβ CDR3 repertoires in both groups were mainly composed of 13-, 14-, and 15-amino-acid sequences. This study provides preliminary, hypothesis-generating evidence that peripheral blood TCRβ CDR3 repertoire features may differ between MDR-TB and DS-TB patients. Larger cohorts including healthy controls and independent functional validation are required before disease-specific or antigen-specific conclusions can be drawn.