Human natural killer cell diversity
Abstract/Contents
- Abstract
- Natural killer (NK) cells are a unique lymphocyte lineage with remarkable agility in the rapid destruction of virus-infected cells. They are also the most poorly understood class of lymphocyte. A spectrum of activating and inhibitory receptors at the NK cell surface leads to an unusual and difficult-to-study mechanism of cellular recognition, as well as a very high capacity for diversity at the single-cell level. Here, we provide the first examination of human natural killer cell repertoire diversity. Using mass cytometry, we identify an unanticipated level of single-cell diversity within and among human subjects. In a study of monozygotic twins, we show that inhibitory receptor expression is determined primarily by genetics, while activating receptor expression is environmentally influenced. This study shows that the human NK cell repertoire is extremely diverse, with both genetic and environmental influences. We further show that this diversity is not limited to NK cells. NK receptors actually become less specific for NK cells as the immune repertoire matures. These receptors are also expressed on T cells, B cells, and monocytes, with cell type-specific changes observed upon maturation. NK cells acquire primarily inhibitory receptors when they mature, while CD8+ T cells acquire both activating and inhibitory receptors. These results show that the expression of NK receptors on multiple cell types is coordinately regulated. In a final study, we show that NK diversity is low at birth, increases by adulthood, and is stable over at least 6 months in healthy adults. It also increases in culture in response to interaction with virally infected cells. Furthermore, in a cohort of Kenyan women, a higher pre-infection level of NK diversity is predictive of a higher likelihood of HIV-1 acquisition. This data shows that NK cell diversity has functional significance and appears to be detrimental in the setting of viral acquisition. We conclude by reviewing outstanding questions in the nascent field of NK cell repertoire diversity. Finally, we look to the future, where emerging single-cell technologies will enable a new generation of rigorous and clinically relevant studies of NK cells accounting for all of their unique and diverse characteristics.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Strauss-Albee, Dara |
|---|---|
| Associated with | Stanford University, Department of Immunology. |
| Principle advisorf4ths | Blish, Catherine |
| Advisor | Krams, Sheri Michele |
| Advisor | Nolan, Garry P |
| Advisor | Parham, Peter, 1950- |
| Thesis advisor | Krams, Sheri Michele |
| Thesis advisor | Nolan, Garry P |
| Thesis advisor | Parham, Peter, 1950- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Dara Strauss-Albee. |
|---|---|
| Note | Submitted to the Department of Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Dara Marie Strauss-Albee
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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