Xingzhu Liu, Chuxiong Gong, Tingting Hao, Jun Li, Xing Zhang, Zhongjian Su, Yanfei Chen, Yangfei Yang, Yuqin Wu
Pediatric MP pneumonia is associated with distinct compartment-specific TCR β repertoire features, including altered repertoire diversity, biased TRBV/TRBJ gene usage, and compartment-dependent CDR3 characteristics, providing insight into systemic and local adaptive immune responses during MP infection.
BACKGROUND: Mycoplasma pneumoniae (MP) is a leading cause of community-acquired pneumonia in children, yet the characteristics of the T cell receptor (TCR) repertoire in the local pulmonary environment remain poorly defined.
METHODS: Paired PBMC and bronchoalveolar lavage fluid (BALF) samples from four MP-infected children were subjected to TCR β CDR3 repertoire sequencing, followed by analysis of clonotype diversity, repertoire overlap, V/J gene usage, CDR3 length distribution, database annotation and k-mer profiling. The main findings were further validated in an independent cohort including 13 MP patients and 20 healthy children (HC).
RESULTS: Although BALF contained fewer clonotypes than paired PBMC samples, it showed a trend toward a higher proportion of recurrent clonotypes and long (≥16 AA) CDR3 sequences. Only a small fraction of clonotypes were shared between paired PBMC and BALF samples, with minimal inter-individual overlap; however, V and J gene usage patterns were more similar within paired samples than between different individuals. A minority of shared clonotypes matched known antigen-specific sequences, mainly against viruses, and k-mer analysis revealed distinct motif patterns in BALF. In the expanded cohort, repertoire diversity was significantly reduced in both MP_BALF and MP_PBMC compared with HC_PBMC. Several TRBV and TRBJ genes showed differential usage between MP patients and healthy controls, and the proportion of long (≥16 AA) CDR3 sequences was significantly increased only in MP_PBMC. Recurrent clonotypes identified in BALF also showed a trend toward higher frequencies in MP_PBMC than in HC_PBMC.
CONCLUSION: Pediatric MP pneumonia is associated with distinct compartment-specific TCR β repertoire features, including altered repertoire diversity, biased TRBV/TRBJ gene usage, and compartment-dependent CDR3 characteristics, providing insight into systemic and local adaptive immune responses during MP infection.