New Type of T Cell

Biologists have analyzed T cells from the gray short-tailed opossum (Monodelphis domestica) and uncovered a previously unknown lineage, called γµ T cells, in the marsupial’s spleen.

Scanning electron micrograph of a human T cell. Image credit: NIAID.

The immune systems of all vertebrates contain T cells that play a fundamental role in protecting against fungal, bacterial, parasitic and viral infections.

These cells use molecular sensors called T cell receptors (TCRs) on their surface that can detect and eliminate the invading pathogens.

For most of the past four decades, it was considered that there were only two T cell lineages, αβ and γδ T cells, characterized by their cell surface expressed αβ and γδ TCRs, respectively.

Evidence for the γμ TCR came with the discovery of genes encoding the TCRμ protein whilst analyzing the genome of the gray short-tailed opossum.

Oddly, distinct from conventional αβ and γδ TCRs, TCRμ was predicted to share similarity with the antibodies.

“The discovery of a nanobody like structure in the γμ TCR has the potential to expand the immunology toolbox,” said Dr. Marcin Wegrecki, a researcher at the Biomedicine Discovery Institute at Monash University.

Dr. Wegrecki and colleagues obtained a detailed 3D image of the opossum γµTCR architecture that was unique and distinct from αβ or γδ TCRs.

Noteworthy was the presence of an additional single antibody-like segment called Vμ domain with an architecture resembling to nanobodies, a unique type of antibodies.

This discovery raises the possibility that γμ T cells recognize pathogens using novel mechanisms, distinct from conventional T cells.

“Our findings further illustrate the value of exploring the world’s biodiversity for novelty beyond the standard animal research models, such as laboratory mice,” said Professor Robert Miller, a researcher in the Department of Biology at the Center for Evolutionary and Theoretical Immunology at the University of New Mexico.

“Modern genomic tools applied to many species have opened the door to the myriad of immunological solutions to fighting pathogens that evolution has produced.”

“Our work may guide the development of veterinary approaches (e.g. novel vaccines) that will contribute to wildlife conservation,” said Dr. Jérôme Le Nours, a researcher at the Biomedicine Discovery Institute and the Australian Research Council Centre of Excellence in Advanced Molecular Imaging at Monash University.

“This is a prime example of curiosity driven science leading to unexpected and transformative findings.”

The discovery is reported in a paper in the journal Science.

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Kimberly A. Morrissey et al. 2021. The molecular assembly of the marsupial γμ T cell receptor defines a third T cell lineage. Science 371 (6536): 1383-1388; doi: 10.1126/science.abe7070