THE THIRD DOMAIN OF T CELLS
Rob Miller, University of New Mexico
Center for Evolutionary and Theoretical Immunology, Department of Biology, University of New Mexico, Albuquerque, NM
Conventional T cells are characterized as being either αβ T cells or γδ T cells based on the composition of their T cell receptor (TCR). All jawed-vertebrates, with the possible exception of squamate reptiles, have both αβ and γδ T cells. In addition to αβ and γδ T cells, the noneutherian mammals (marsupials and monotremes) have a third lineage, the γμ T cell. TCRμ has a distinct genomic organization and encodes a third immunoglobulin domain in the extracellular chain. To investigate the function of γμ T cells, single cell RNA sequencing was performed on opossum splenocytes. γμ T cells make up approximately 10% of splenocytes in the opossum, are the second most common T cell in the spleen after αβ T cells, and appear to be absent from peripheral blood. γμ T cells have a distinct transcriptome, relative to αβ T cells. Transcriptome analyses reveal that a majority of γμ T cells are CD8+ but express CD8 in the CD8αα form. None are CD4+. In addition, γμ T cells express an unusual combination of killer associated markers and, curiously, olfactory receptors. Globally, the transcriptomes of γμ T cells are highly distinct from that of αβ T cells. Opossum γδ T cells however are a split group, sharing features of γμ T cells and some αβ T cells. In summary, γμ T cells are an ancient T cell type in mammals, that was lost in the eutherians (e.g. humans), whose function is unknown but appears distinct from conventional T cells.