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January 12, 2022

The Power of Tetramers: A Tool Developed by Bill Kwok, PhD

Bill Kwok, PhD, has made groundbreaking discoveries and built a tool that’s fueled countless advances. But he makes his work and his path to BRI sound simple: Why study the minute details of the immune system? Well, he’s curious — he was always at the library as a kid. Why leave his native Hong Kong as a teenager? Well, his sister went to the University of Wisconsin which had a good reputation, so why not go there. Why come to Seattle and ultimately join BRI, then a brand-new institute?

Bill Kwok
Bill Kwok, PhD

“Well, Wisconsin was too cold,” Dr. Kwok says. “And Jerry Nepom, MD, PhD, seemed like a good person to work with.”

When Dr. Kwok joined Dr. Nepom’s lab in the 1980s, immunology was a new field. Little was known about immune cells and molecules.

“To study rare and specific immune cells, we needed a way to find and isolate them,” Dr. Kwok says.

This immensely complex scientific challenge went unsolved — until the 1990s.

“It required a tour de force of molecular engineering. And Bill figured it out,” Dr. Nepom says. “This major breakthrough allowed us to see these cells and study how they trigger immune responses.”

This tool, MHC class II tetramers, first helped Dr. Kwok’s team study rare immune cells in influenza. Then they sorted through millions of immune cells to pinpoint the few involved in autoimmune disease — seeing and studying them for the first time.

“In addition to making significant contributions to the field, Bill is a great teacher,” Dr. Nepom says. “The scientists he’s mentored, like Erik Wambre, PhD, and Eddie James, PhD, have expanded BRI’s work and made important contributions of their own.”

Three decades later, Dr. Kwok is still investigating immune cells, currently examining those that respond to COVID-19 vaccines and that contribute to peanut allergy and T1D. Curiosity still motivates him, and one question in particular keeps him up at night: Why do some people with certain genes get T1D while others with the same genes don’t?

“We have some general ideas but we still need to work out the details of the role HLA genes play in T1D susceptibility,” Dr. Kwok says.

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