Posted on July 7, 2004 at 5:00 p.m.
BIRMINGHAM, AL — A research team led by the University of Alabama at Birmingham (UAB) scientist who helped define the human immune system in the mid-1960s has discovered a new type of immune system in the sea lamprey. The work, which may be useful in disease diagnosis and treatment, is being published July 8 as the cover story in the journal Nature.
Dr. Max D. Cooper, UAB professor of medicine and pediatrics and a Howard Hughes Medical Institute investigator; post-doctoral student Zeev Pancer, Ph.D., first author on the paper; and other colleagues wrote that remnants of the primordial immune system of the sea lamprey might have survived in humans and other higher organisms. The jawless vertebrate “has a radically different immune system than humans and other jawed vertebrates, but it may offer the same protection in recognizing invaders and alerting damage-control elements,” Cooper said.
The sea lamprey, a jawless vertebrate, is more primitive than jawed vertebrates. Lampreys and hagfish are the only surviving descendants from the earliest evolution of vertebrates. The researchers found that the lampreys use a set of genes that they named variable lymphocyte receptors (VLRs). The VLRs consist of various combinations of segments called leucine rich repeats (LRRs), and a region that attaches a receptor to the surface of each lamprey lymphocyte.
This is the first animal in which it’s known that LRR gene rearrangements are used to form adaptive immune system proteins, Cooper said.
“The second big surprise was that we found only a single VLR locus on the lamprey chromosomes, not multiple ones,” he said. “And this locus contained only one VLR gene that is incomplete. The incomplete VLR is flanked by LRR sequences that are somehow stitched into the incomplete VLR gene to make a mature VLR gene.
“It looks as if nature experimented with different ways to build highly diverse receptors to use for anticipatory systems to recognize potential pathogens,” Cooper said. “And nature invented the LRR rearrangement system prior to when the one that we use was invented.”
Does the ancient immune system survive in humans or other higher vertebrates? “It seems unlikely that nature would have generated such a complicated system and then quickly thrown it away, so we are looking in higher organisms to see how long this variable system lasted in evolution,” he said. “It’s also possible that these VLRs could be used for the same practical purposes as antibodies — to recognize a variety of different antigens and pathogens.”
In the mid-1960s Cooper, a developmental immunologist, worked with others to delineate T and B cells in birds and mammals. “How the discovery of another kind of adaptive immune system will affect us is not as clear as the implications of the T and B cell split were, but it does open up exciting theoretical paths,” he said.
Others on the research team are Chris T. Amemiya of the Benaroya Research Institute at Virginia Mason in Seattle; Jill Ceitlin of the University of Michigan, who was a summer student in Cooper’s lab; and Gotz R. A. Ehrhardt and G. Larry Gartland of UAB.