Scientists Discover Unique New T Cell Receptor In Marsupial Research (6/10/2007)

Photo Credit: UMN

Opossums are soft and furry, cute and cuddly looking and they could open up a new way in which critical cell types in the immune system called T cells, may be seeing pathogens based on new genome sequencing research involving scientists in the University of New Mexico's Biology department. The research, which is funded largely by the National Science Foundation, is set to be released in the June issue of the magazine PNAS, the Proceedings of the National Academy of Sciences.

The scientists include lead author and UNM Ph.D. student Zuly Parra, Michelle Baker, research assistant Professor, Ryan Schwarz, Ph.D. student and Professor Robert Miller, in collaboration with researchers from the Australian National University and the Broad Institute, have discovered a fifth such chain, designated "mu," (for marsupial) that has been discovered in opossums.

T cells are a responsible for activating many aspects of the immune response. They do this job by recognizing specific pathogens or antigens using receptors, called T cell receptors, present on their cell surface. In the mid-80s, four proteins that make up the T cell receptor called alpha, beta, gamma and delta were discovered. By the mid-90s, research had shown that all vertebrates, from humans to sharks, had the same homologous four molecules. Until now immunologists thought that alpha, beta, gamma and delta were all there was.

"The significance is that it opens up a whole new way in which T cells in some species may be seeing pathogens," said Miller. "It may also represent novel adaptations in other distantly related species. The discovery came out of genomic analysis of marsupials and illustrates the value of looking at the genomes of more species for novelty."

The process, called shotgun sequencing, involves the DNA from a single animal. Researchers basically fragment the DNA into smaller bits and clone into libraries and sequence into smaller fragments that overlap each other. When they are done with the sequencing, they assemble the sequence based on the overlaps and reconstruct the chromosomes that way.

In Miller's lab, their interests are in the genes of the immune system. The receptors the immune system recognizes are called pathogens. There are three kinds of receptors including the major histocompatibility complex, which are genes they type you for if you want to be an organ donor; another receptor gene are antibodies which are familiar to most people; and also T cell receptors.

Miller, who has been funded for marsupial immune systems research by the NSF since 1995, recently received another NSF grant through 2011 to continue his research. Some additional funding came through the National Institute of Health (NIH) Center for Biomedical Research Excellence (COBRE) program in "Evolutionary and Theoretical Immunology" the UNM biology department received. His group was studying and characterizing T cell receptors when the new gene discovery was made.

"Opossums are actually used as a model for human melanoma. T cells are important in cancer and we were interested in learning more about the T cell receptors," he said. "While we were conducting that research, we came across this extra one (gene), which caught our attention because it looked different. We found parts that looked more like antibodies and other parts that looked more like T cell receptors. We know it was a T cell receptor because the definition of a T cell says it develops in the thymus.

"As the T cells are developing, the genes undergo rearrangements. Each T cell does its own unique rearrangement and that's how each T cell gets specific for its own pathogen or antigen. We knew the rearrangements were taking place in the thymus and that defined it as a T cell receptor," Miller said.

"It has these aspects that make it look more like antibodies which probably tells us it probably recognizes antigens perhaps more the way an antibodies do than the way a normal conventional T cell receptors do even though it's used by a T cell."

Miller says that while the gene is not found in humans, mice or any other placental mammal that has been looked at, he did point out that a colleague at the University of Maryland recently found a similar gene in sharks that looks "a little like this" although not identical.

"It's not the same set of genes," Miller said. "But there's what we refer to as converging evolution. Sharks have come up with this gene independently as well. So if it's in marsupials, and if it's in sharks, then one suspects it's going to be other places too. We just haven't found it yet."

Note: This story has been adapted from a news release issued by the University of New Mexico

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