Lamprey Antibodies Useful?
Adaptive Immune System Is Millions of Years Old, Cooper Finds
Our adaptive immune system’s ability to remember pathogens it previously encountered depends upon 2 types of lymphocytes called T and B cells, which may have arisen 500 million years ago, said Dr. Max Cooper at the William E. Paul Lecture, Cooper’s first major talk since winning the 2019 Albert Lasker Basic Medical Research Award.
“What these cell types were using for antigen recognition before then is one of many unanswered questions,” said Cooper, a professor of pathology and laboratory medicine at Emory University School of Medicine and a Georgia Research Alliance eminent scholar. He spoke in Masur Auditorium on Oct. 2.
To find answers, his lab studies sea lampreys, an ancient jawless predator that has proven to have a sophisticated immune system. Sea lampreys have rasp-like tongues and rings of sharp teeth they use to latch onto their prey. The animal is famous for being an invasive inhabitant of the Great Lakes. Each adult sea lamprey can kill roughly 35 kilograms of fish in a year. The jawless vertebrates—lampreys and hagfish—are thought to have diverged from the jawed vertebrates more than 500 million years ago.
“We couldn’t go back and look at the earliest jawed vertebrate representatives. Because they had all died out by around 360 million years ago, we know about them only through their fossilized remains,” Cooper said.
The two types of white blood cells called B and T lymphocytes are the major components of the jawed vertebrates’ adaptive immune system. Both types of lymphocytes are derived from stem cells located in the bone marrow. Once B cells develop from their bone marrow precursors, they circulate throughout the body. Mature B cells have surface antigen-specific receptors, allowing the cell to recognize and bind to invasive pathogens. T cells are also derived from their bone marrow precursors but they mature in a lymphatic organ called the thymus, where they develop a diverse repertoire of receptors, each of which can recognize specific antigens.
Lampreys lack the cardinal features of the antigen receptor system found in all of the jawed vertebrates’ adaptive immune system, Cooper said. Lampreys instead produce variable lymphocyte receptors (VLRs) by assembling different combinations of leucine-rich repeat proteins to create a vast repertoire of receptors to recognize and fight against specific pathogens.
At one time, jawed and jawless vertebrates shared a common ancestor, but Cooper believes that due to subsequent convergent evolution—the process where organisms independently evolve different solutions to achieve the same function—the two types of vertebrates evolved different types of antigen receptors. Since lamprey VLRs have unique antigen specificities, Cooper hopes to use the lamprey VLR antibodies for diagnosis and potential treatments for cancer. “When we first saw this unexpected VLR diversity, the light came on for us. Although this was not what we started out looking for, we realized that this remarkable variability could be the basis for a recognition system that could discriminate between different antigens,” he said.
The Paul lecture honors the legacy of Dr. William E. Paul, who was the leader of the NIH immunology community. The lecture recognizes outstanding contributions in immunology.