>>A spineless sea creature yields new clues to evolution of modern immunity

USF Health geneticist Gary Litman's research funded by NIH

Tampa, FL (August 22, 2006) -- A University of South Florida geneticist’s research using a primitive marine creature – a good smaller-scale model for human immunity – continues to yield intriguing insights into the evolutionary bridge between innate and adaptive immunity. The work of Gary Litman, PhD, the Hines Professor of Pediatrics at USF Health, and others could help shed light on how the immune system is compromised by pathogens or genetic defects, and ultimately may lead to better therapies for allergic and autoimmune diseases such as lupus and rheumatoid arthritis.

 

A paper recently co-authored by Dr. Litman bolsters an emerging theme that the systems effecting basic immunity and those using genetic rearrangement to prompt massive diversity in immune molecules arose far earlier in evolution than previously considered. The study, “Ancient evolutionary origin of diversified variable regions demonstrated by crystal structures of an immune-type receptor in amphioxus,” appears in the August 2006 issue of the journal Nature Immunology, accompanied by a News and Views commentary. Other USF authors were Robert Haire, PhD, and John Cannon, PhD, both of the Department of Pediatrics.

 

Researchers at the University of Florida, USF, Moffitt Cancer Center and Brookhaven National Laboratory analyzed the 3-dimensional structure of immune-type molecules known as VCBPs (variable region-containing chitin-binding proteins) in amphioxus, a protochordate that physically resembles a worm and is poised on the evolutionary threshold between invertebrates and vertebrates. They found that the 3-D structure of this lowly marine creature’s VCBPs were remarkably similar to the antibody and T-cell antigen receptors that are the primary immune recognition molecules in humans.

 

"It is ironic that in the process of examining these structures, we were able to produce crystals of such extraordinary quality that we could recognize heretofore unseen structural features that likely impact the functioning of our immune receptors,” said Dr. Litman, whose laboratory is based at the USF/All Children’s Hospital Children’s Research Institute in St. Petersburg. “Among other things, our immune receptors recognize bacteria and viruses."

 

Immunity refers to the global ability of a host to resist the attacks of microbes that would otherwise destroy it. The natural, or innate, immunity of amphioxus and other invertebrates is characterized by preformed receptors and provides an immediate first line of defense against microorganisms. In addition to innate immunity, humans and other jawed vertebrates have evolved more customized, or adaptive, immune responses in which a complex arsenal of antibodies and T-cell receptors, and an even more elaborate process of clonal selection, fends off diverse pathogens and prevents repeat attacks.

 

“The VCBPs show us the bridge between the static receptors of the innate system and the rearranging receptors of the adaptive system that is being played out in an equivalent structure,” Dr. Litman said. “It is possible that the VCBPs represent the missing link in our understanding of how our modern adaptive immune system arose.”

 

Dr. Litman, whose research in this area has been funded for 26 consecutive years by the National Institutes of Health, is often sought to comment on scientific papers of merit in the field of immunity.

 

His commentaries and reviews recently appeared in three high-impact journals -- a Previews article in Immunity (“How Botryllus Chooses to Fuse,” July 25, 2006), a News & Views for Nature (“Histocompatibility: Colonial Match and Mismatch,” Nov. 25, 2005), and a Nature Immunology Reviews (“Reconstructing Immune Phylogeny: New Perspectives,” November 2005). He comments on alternative systems of immune function related to tissue transplantation and stem cell survival, underscoring the important role for innovative new animal models in improving the understanding of human health and disease.

 

 

 

- USF Health -

 

USF Health is the University of South Florida’s partnership of the Colleges of Medicine, Nursing and Public Health, the School of Basic Biomedical Sciences, the School of Physical Therapy and Rehabilitation Sciences, as well as the USF Physicians Group. USF Health’s research funding last year was $134 million – more than half of which came from federal sources. Last year, USF Health clinicians cared for more than 31,000 patients and oversaw 396,000 patient visits.