3 years ago

TCR-pMHC encounter differentially regulates transcriptomes of− tissue-resident CD8 T cells

Bruce Reinhold, Kevin Bi, Derin B. Keskin, Akihiro Yoshikawa, Ellis L. Reinherz, Guanglang Zhang
To investigate the role of TCR-pMHC interaction in regulating lung CD8 tissue-resident T cell (TR) differentiation, polyclonal responses were compared against NP366-374/Db and PA224-233/Db, 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 TR generation and intraepithelial translocation. Gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) identify dominant TCR, adherence junction, RIG-I-like and NOD-like pattern recognition receptor as well as TGFβ signaling pathways and memory signatures among PA224-233/Db T cells consistent with T resident memory (TRM) status. In contrast, NP366-374/Db T cells exhibit enrichment of effector signatures, upregulating pro-inflammatory mediators even among TRM. While NP366-374/Db T cells manifest transcripts linked to canonical exhaustion pathways, PA224-233/Db T cells exploit P2xr7 purinoreceptor attenuation. The NP366-374/Db CD103+ subset expresses the antimicrobial lactotransferrin whereas PA224-233/Db 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 TR and antigen presenting cells in a tissue milieu strongly impact CD8 T cell biology. This article is protected by copyright. All rights reserved

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/eji.201747174

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