In search of the ‘missing self’: MHC molecules and NK cell recognition
Abstract
Natural killer (NK) cells can defend an organism against a variety of threats, probably using several different strategies to discriminate between normal and aberrant cells. According to the 'missing self' hypothesis, one function of NK cells is to recognize and eliminate cells that fail to express self major histocompatibility complex (MHC) class I molecules. In this article Hans-Gustaf Ljunggren and Klas Kärre review in vivo studies with H-2-deficient targets that support this hypothesis. In vitro studies, some of which have given conflicting results, are interpreted within a multiple choice model for NK cell recognition. The authors derive testable predictions for how MHC class I molecules act in cases where they control a rate-limiting step in the NK cell-target interaction.
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Absence of MHC-I on the target cell triggers killing of that cell.
“However, the absence of MHC-I on the target cell instead triggers the killing of that cell (65).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [65]
Tolerance toward cells recognised as 'self' is assured upon recognition of MHC-I on the target cell surface through inhibitory Killer Ig-like receptors or upon binding of the heterodimer CD94/NKG2A to HLA-E.
“The tolerance toward cells recognised as 'self' is assured upon the recognition of MHC-I on the target cell surface through the inhibitory Killer Ig-like receptors or upon binding of the heterodimer CD94/NKG2A to HLA-E (65, 66).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [65]
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References 82 · Cited by 2,687
- Authors
- Ljunggren, H.-G., & Kärre, K.
- Affiliations
- Karolinska Institutet (SE)
- Venue
- Immunology Today
- Publisher
- Elsevier BV
- Published
- 1990-01
- Volume
- 11
- Issue
- 7
- Pages
- 237-244
- ISSN
- 0167-5699 (ISSN-L)
- OpenAlex
- W2005765588
- Cited by
- 2,687
- References
- 82
- Citations by year
- 2026: 50 · 2025: 66 · 2024: 68 · 2023: 66 · 2022: 89 · 2021: 105 · 2020: 89 · 2019: 78 · 2018: 73 · 2017: 80 · 2016: 72 · 2015: 82 · 2014: 77 · 2013: 105 · 2012: 71
- FWCI
- 17.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Immunology Today (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- natural killer cells, MHC class I, NK cell recognition, rate-determining step, self-tolerance, cytotoxicity
- MeSH terms
- Animals, Antigens, Neoplasm, Crosses, Genetic, Cytotoxicity Tests, Immunologic, Genes, MHC Class I, Graft Rejection, H-2 Antigens, Humans, Immune Tolerance, Killer Cells, Natural, Models, Biological, Research Design, Transfection, Tumor Cells, Cultured, Histocompatibility Antigens Class I, Gene Expression Regulation, Neoplastic, Mice, Rats
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