TCR Specificity Dictates CD94/NKG2A Expression by Human CTL
Open accessAbstract
Activating and inhibitory CD94/NKG2 receptors regulate CTL responses by altering TCR signaling, thus modifying antigen activation thresholds set during thymic selection. To determine whether their expression was linked to TCR specificity, we examined the TCR repertoire of oligoclonal CTL expansions found in human blood and tissues. High-resolution TCR repertoire analysis revealed that commitment to inhibitory NKG2A expression was a clonal attribute developmentally acquired after TCR expression and during antigen encounter, whereas actual surface expression depended on recent TCR engagement. Further, CTL clones expressing sequence-related TCR, and therefore sharing the same antigen specificity, invariably shared the same NKG2A commitment. These findings suggest that TCR antigenic specificity dictates NKG2A commitment, which critically regulates subsequent activation of CTL.
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In healthy individuals, CD8αβ+ TCRαβ+ IELs express the inhibitory NK receptors CD94/NKG2A, with a low expression of activating receptor NKG2D.
“In healthy individuals, CD8αβ+ TCRαβ+ IELs express the inhibitory NK receptors CD94/NKG2A, with a low expression of activating receptor NKG2D [304, 305].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [305]
The Results passage on CD94 and NKG2 isotypes (page unavailable) identifies a CD8+ TCRαβ+ IEL subset expressing inhibitory CD94/NKG2A. It also identifies NKG2A-negative IELs, so the finding does not apply to all such IELs. The copy does not report low NKG2D expression; its mention of NKG2D is in a reference title. (LLM, conf=0.88)
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- Authors
- Jabri, B., Selby, J. M., Negulescu, H., Lee, L., Roberts, A. I., Beavis, A., Lopez-Botet, M., Ebert, E. C., & Winchester, R. J.
- Affiliations
- Columbia University (US)
- Princeton University (US)
- University of Medicine and Dentistry of New Jersey (US)
- Corresponding author
- Winchester, Robert J
- ORCID
- Winchester, Robert J
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2002-10
- Volume
- 17
- Issue
- 4
- Pages
- 487-499
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2136981663
- Cited by
- 136
- References
- 46
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 10 · 2023: 5 · 2022: 1 · 2021: 10 · 2020: 4 · 2019: 4 · 2018: 7 · 2017: 2 · 2016: 3 · 2015: 8 · 2014: 3 · 2013: 6 · 2012: 4
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Update notices
- erratum (2002-12-01)
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3942 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (ACE U19 AI46132, DK 42166-11, FIS 00/0181, RO1 DK 58727-01A1, SAF2001/0696)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CD94/NKG2A, NKG2A, T cell receptor specificity, cytotoxic T lymphocytes, inhibitory receptors, T cell receptor repertoire, clonal expansion, thymic selection, T cell receptor signaling, NK cell receptors
- MeSH terms
- Amino Acid Sequence, Base Sequence, Cell Line, Clone Cells, DNA, Humans, Lymphocyte Activation, Molecular Sequence Data, Receptors, Immunologic, T-Lymphocytes, Cytotoxic, Signal Transduction, Antigens, CD, Gene Expression, T-Lymphocyte Subsets, Models, Immunological, Lectins, C-Type, T-Cell Antigen Receptor Specificity, NK Cell Lectin-Like Receptor Subfamily D, Receptors, Natural Killer Cell, NK Cell Lectin-Like Receptor Subfamily C
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