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

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.

• 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)
• 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

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)