Exploring the Functions of NK Cells in Innate and Adaptive Immunity

Natural Killer (NK) cells are the innate immune system’s first and best defense against infections. Unlike cytotoxic T cells in the adaptive immune system that require genetic matching with the target cell, NK cells are pre-programmed with cytotoxic granules that can kill any type of infected target cell.

The ability to rapidly respond to an infection makes NK cells the logical choice for research in antibody-based therapeutics.

Let’s take a closer look at a few functions of NK cells and their role in current research.

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Recognizing “Missing Self” Cells & ADCC

Immune cells, including NK cells, typically detect major histocompatibility complex (MHC) bound to the surface of infected cells to trigger cytokine release and subsequent cell death. While NK cells do recognize MHC, they are also capable of recognizing cells that do not express MHC or express MHC that isn’t theirs.

NK cells can also recognize target cells that are coated with antibody using their Fc receptors to bind to the antibody and trigger cell death in a process known as antibody-dependent cell-mediated cytotoxicity (ADCC). Several antibody-based treatments, including Herceptin and Rituxan, use this pathway to target infected cells. NK cells are indispensable for testing the ADCC of an antibody in developing antibody-based therapeutics.

The ability to target and kill cells that are missing their “self” markers allows for a much quicker immune response, which other immune cells are not capable of producing because they cannot determine if a cell is infected or not.

Certain tumor cells or virus-infected cells can circumvent other immune cells, so NK cells have adapted to destroy such deceptive and harmful pathogens.

Genetic Variations in Fc Receptors

All NK cells express the Fc receptor FcγRIII (CD16), although there are genetic variations. FcγRIII plays a critical role in ADCC, in particular in binding to Immunoglobulin G (IgG). The amino acid at position 158 of the protein can either be coded as phenylalanine (F) or valine (V).

Individuals who have two copies that code for V will bind antibody better than individuals who have two copies that code for F. Some published studies suggest that patients who are V/V respond better to treatment with antibody therapies than F/F patients. Patients who are F/V have intermediate responses.    

We check for this gene in our NK cell donors so we can provide you with donors expressing each of these three allele types (F/F, V/V, and F/V). This should help you predict how well the cells will perform in your ADCC assay.

Adaptive “Memory-Like” NK Cells

Generating memory cells is traditionally a role played by B cells and T cells in the adaptive immune system. However, research has shown that NK cells can exhibit similar adaptive behaviors, such as clonal expansion, increased longevity, and a more potent response upon secondary challenge.

Adaptive NK cell activity has been observed in response to infections such as CMV, Hantavirus, Chikungunya virus, HIV, and hepatitis, although this is a current area of study.

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Cytotoxicity of Our NK Cells

We have tested our NK cells to ensure their in vitro lytic activity by labeling target cells with CFSE. In the histograms below, lysis was evident at all ratios with maximum cell killing observed at a 10:1 NK:K562 ratio.

Natural Killer (NK) Cells Assay

3 New NK Cell Donors

We recently added three new NK cell donors to our inventory. Each has a detailed Certificate of Analysis with cell counts, viability, full donor information, and HLA typing.

New donors include a healthy, B positive, 52-year-old, Caucasian male (F/F); a healthy, A positive, 51-year-old, Caucasian female(F/V); and a healthy, A positive, 24-year-old, Caucasian male(F/V).

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