Abstract |
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, adherens junction, RIG-I-like and NOD-like pattern recognition receptor as well as TGF-β 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 P2rx7 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.
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Authors | Akihiro Yoshizawa, Kevin Bi, Derin B Keskin, Guanglan Zhang, Bruce Reinhold, Ellis L Reinherz |
Journal | European journal of immunology
(Eur J Immunol)
Vol. 48
Issue 1
Pg. 128-150
(01 2018)
ISSN: 1521-4141 [Electronic] Germany |
PMID | 28872670
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Chemical References |
- Antigens, CD
- Epitopes, T-Lymphocyte
- Integrin alpha Chains
- NLR Proteins
- Receptors, Antigen, T-Cell, alpha-beta
- Transforming Growth Factor beta
- alpha E integrins
- DEAD Box Protein 58
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Topics |
- Animals
- Antigens, CD
(biosynthesis)
- CD8-Positive T-Lymphocytes
(immunology)
- Cell Differentiation
(immunology)
- DEAD Box Protein 58
(metabolism)
- Epitopes, T-Lymphocyte
(immunology)
- Female
- Immunologic Memory
(immunology)
- Influenza A Virus, H1N1 Subtype
(immunology)
- Integrin alpha Chains
(biosynthesis)
- Lung
(cytology, immunology)
- Mice
- Mice, Inbred C57BL
- NLR Proteins
(metabolism)
- Orthomyxoviridae Infections
(immunology)
- Receptors, Antigen, T-Cell, alpha-beta
(genetics, immunology)
- T-Lymphocyte Subsets
(immunology)
- Transforming Growth Factor beta
(metabolism)
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