Journal News

MCP: This protein makes
antibody drugs work

Laurel Oldach
Nov. 1, 2019

Hundreds of therapeutic antibody drugs target cell-surface molecules in cancers and other diseases. But different patients respond differently to antibody therapy, and doctors struggle to predict who will benefit most.

CD 16 receptors
An artist’s rendering shows CD16 receptors on a natural killer cell (blue) binding to the constant region of an antibody (orange) that also is bound to a target molecule.

Except for a few used to ferry drugs or toxins to a specific cell population, most antibodies work by recruiting the immune system. When natural killer cells, the body’s tiny assassins, recognize antibodies coating a target cell, the NK cells latch onto the target and kill it.

Kashyap Patel, a grad student at Iowa State University, studies the receptor CD16a, receptor protein on natural killer cells that recognizes and binds to antibodies. Patel and his advisor, Adam Barb, now a professor at the University of Georgia, were interested in changes to CD16a that might underlie binding changes.

“CD16a in our bodies is different than the CD16a that’s used to test monoclonal antibodies,” Patel said. Whereas the recombinant version used in laboratories has limited posttranslational modifications, the human version is glycosylated at five different sites. Glycosylation, which happens in the endoplasmic reticulum, can add complex branched structures to a protein; those modifications can alter proteins’ binding characteristics and could in principle make CD16a more or less likely to bind to antibodies.

Scientists know that a genetic polymorphism near one N-glycosylation site in CD16a can influence how well antibody treatment works. It isn’t clear whether that polymorphism affects glycans directly or whether genetic changes that do affect glycans affect CD16a-antibody binding. Studying the variations in glycan structure at each site is difficult, because isolating enough CD16a from a single person to analyze poses a technical challenge.

In a recent article in the journal Molecular & Cellular Proteomics, Patel, Barb and colleagues report that they studied post-translational modifications to CD16a in glycopeptide samples harvested from the natural killer cells of individual plasma donors. Then they used glycomics tools to determine the structures of the glycans.

“We weren’t expecting the variability we saw,” Patel said. At five sites in CD16a, the team found substantial variability in the structure of glycans — both among the donors and within each individual.

The researchers don’t know yet what to make of the glycan variability, because the donor pool was small and few studies of this type have been done. However, now that the protocol for studying glycan composition from a single person is worked out, Barb’s lab hopes to determine whether changes to that composition affect the immune system’s response to antibody therapy.

When Patel started this project, he didn’t know much about protein glycosylation, but he said he intends to keep studying it as a postdoctoral fellow.

“Once you see a protein with N-glycans on it, you cannot unsee it. You can’t ignore it.”

Enjoy reading ASBMB Today?

Become a member to receive the print edition four times a year and the digital edition weekly.

Learn more
Laurel Oldach

Laurel Oldach is a former science writer for the ASBMB.

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

Beneficial gut microbe has surprising metabolic capabilities
News

Beneficial gut microbe has surprising metabolic capabilities

Nov. 23, 2024

WashU researchers’ mouse study of therapeutic food for malnourished children shows a new gut bacterial enzyme's wide-ranging functions.

Transforming learning through innovation and collaboration
Award

Transforming learning through innovation and collaboration

Nov. 22, 2024

Neena Grover will receive the William C. Rose Award for Exemplary Contributions to Education at the 2025 ASBMB Annual Meeting, April 12–15 in Chicago.

From the journals: JBC
Journal News

From the journals: JBC

Nov. 22, 2024

Prefoldins participate in parasite pathology. Protein modifications coordinate in DNA repair. Nucleotide analog blocks viral RNA polymerases. Read about recent papers in the JBC on these topics.

Guiding grocery carts to shape healthy habits
Award

Guiding grocery carts to shape healthy habits

Nov. 21, 2024

Robert “Nate” Helsley will receive the Walter A. Shaw Young Investigator in Lipid Research Award at the 2025 ASBMB Annual Meeting, April 12–15 in Chicago.

Quantifying how proteins in microbe and host interact
Journal News

Quantifying how proteins in microbe and host interact

Nov. 20, 2024

“To develop better vaccines, we need new methods and a better understanding of the antibody responses that develop in immune individuals,” author Johan Malmström said.

Leading the charge for gender equity
Award

Leading the charge for gender equity

Nov. 19, 2024

Nicole Woitowich will receive the ASBMB Emerging Leadership Award at the 2025 ASBMB Annual meeting, April 12–15 in Chicago.