U. PENN (US)—Researchers have identified the function of one of the earliest antibodies in the animal kingdom, an ancient immunoglobulin that helps explain the evolution of human intestinal immune responses.

It plays a predominant role in the guts of fish and paves the way for a better understanding of human gut immunity—as well as for safer, healthier approaches to keeping fish from pathogen infections.

The work is featured on the cover of the September issue of Nature Immunology.

The study identified unique aspects of the structure and function of a fish antibody, IgT, and points to this molecule as the most ancient vertebrate immunoglobulin specialized in mucosal immunity.

The findings challenge the present paradigm that specialization of immunoglobulin isotypes into different body areas (i.e., intestine and blood) arose during the evolution of four-legged creatures, or tetrapods. While IgT was discovered five years ago, its structure and function remained an enigma.

The research team concluded that the specialization of immunoglobulin isotypes into different body compartments is a universal feature of all jawed vertebrate immune systems, a feature required for health maintenance in environmentally different exposed body areas that require different immune needs.

“Immunoglobulins like IgA, IgX and the newly discovered IgT are evolutionarily distant,” says Oriol Sunyer, associate professor in the pathobiology department at the University of Pennsylvania School of Veterinary Medicine.

“Their specialization into mucosal compartments must have occurred independently by a process of convergent evolution driven by similar selective pressures operating on the gut environment of fish, amphibians, and mammals.”

Significantly, the study shows that fish IgT and human IgA systems appear to utilize similar solutions to maintain healthy intestines, therefore Sunyer indicates that “future studies on IgT will further unravel structural and functional aspects of human mucosal immunoglobulins that are key to their role in keeping our intestines free of pathogens.”

With aquaculture being the fastest growing animal food sector in the United States, as well as in the global marketplace, the findings should also impact fish health and vaccinology. In that regard, all prior studies carried out in teleost fish during the last few decades have missed the specific contribution of IgT in protecting fish from pathogens.

The research was funded by the National Science Foundation, the National Institutes of Health, and the United States Department of Agriculture.

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