To investigate the role of TCR-pMHC interaction in regulating lung CD8 tissue-resident T cell (T_{R} ) differentiation, polyclonal responses were compared against NP_{366-374} /D^{b} and PA_{224-233} /D^{b} , two immunodominant epitopes that arise during influenza A infection in mice. Memory niches distinct from iBALTs develop within the lamina propria, supporting CD103^{+} and CD103^{-} CD8 T_{R} generation and intraepithelial translocation. Gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) identify dominant TCR, adherens junction, RIG-I-like and NOD-like pattern recognition receptor as well as TGF-β signaling pathways and memory signatures among PA_{224-233} /D^{b} T cells consistent with T resident memory (T_{RM} ) status. In contrast, NP_{366-374} /D^{b} T cells exhibit enrichment of effector signatures, upregulating pro-inflammatory mediators even among T_{RM} . While NP_{366-374} /D^{b} T cells manifest transcripts linked to canonical exhaustion pathways, PA_{224-233} /D^{b} T cells exploit P2rx7 purinoreceptor attenuation. The NP_{366-374} /D^{b} CD103^{+} subset expresses the antimicrobial lactotransferrin whereas PA_{224-233} /D^{b} CD103^{+} utilizes pore-forming mpeg-1, with <22% of genes correspondingly upregulated in CD103^{+} (or CD103^{-} ) subsets of both specificities. Thus, TCR-pMHC interactions among T_{R} and antigen presenting cells in a tissue milieu strongly impact CD8 T cell biology.
【저자키워드】 T cells, Lung infection, influenza A, GSEA, Trm, TCR-pMHC, TGF-β, Transcriptome,