Signatures of Protective NK Cell Responses

Learn about recent advances in our understanding of NK cell diversity and function

Watch now to learn how mass cytometry is advancing our understanding of natural killer (NK) cell diversity and function by Catherine Blish and colleagues at Stanford.

NK cells play critical roles in immune defense and reproduction but remain the most poorly understood major lymphocyte population. NK cells contribute to control of chronic HIV infection, yet their role in protection from infection and their potential for eradication strategies is less clear. NK cell activation is controlled by a variety of combinatorially expressed activating and inhibitory receptors, making NK cell diversity and function closely linked.

Using mass cytometry to perform high-parameter immunophenotyping, Catherine Blish and colleagues at Stanford recently defined the human NK cell repertoire as remarkably diverse, with an estimated 6,000 to 30,000 phenotypic populations within an individual and >100,000 phenotypes in a small population. Blish presents this data, including additional studies revealing that immune experience diversifies and specializes the NK cell repertoire, and that high NK diversity is associated with increased risk of HIV-1 acquisition in a Kenyan cohort. Overall, these studies suggest that NK diversity may decrease the flexibility of the antiviral response, and that human NK diversity is a previously undefined metric of immune history and function that may be clinically useful in predicting the outcomes of viral exposure.

Michelle Poulin, Fluidigm Field Applications Scientist, also gives a brief overview of mass cytometry, the high-parameter, single-cell technology utilized by Dr. Blish in her NK cell analyses.

Mass cytometry, or cytometry by time-of-flight, the basis of Fluidigm® CyTOF® technology, uniquely enables high-dimensional single-cell proteomic analysis for system-level discovery and comprehensive functional profiling applications. The large 40-plus-marker proteomic panels routinely analyzed using mass cytometry provide simultaneous measurement of the breadth of cell types and the depths of their functions in a single tube. This high-information-per-tube approach is particularly valuable when sample size and resources are limited. This brief overview describes the basic principles and workflow of the technology, including recent advancements.


 Catherine Blish

Catherine Blish, PhD
Assistant Professor, Department of Medicine and Immunology     
Stanford University School of Medicine
Assistant Director of the Stanford Medical Scientist
Training Program (MSTP)

 Michelle Poulin

Michelle Poulin, PhD
Field Applications Scientist