Morrissey, K.A.Sampson, J.M.Rivera, M.Bu, L.Hansen, V.L.Gemmell, N.J.Gardner, M.G.Bertozzi, T.Miller, R.D.2022-05-242022-05-242022Journal of Immunology, 2022; 208(8):1960-19670022-17671550-6606https://hdl.handle.net/2440/135185T lymphocytes or T cells are key components of the vertebrate response to pathogens and cancer. There are two T cell classes based on their TCRs, ab T cells and gd T cells, and each plays a critical role in immune responses. The squamate reptiles may be unique among the vertebrate lineages by lacking an entire class of T cells, the gd T cells. In this study, we investigated the basis of the loss of the gd T cells in squamates. The genome and transcriptome of a sleepy lizard, the skink Tiliqua rugosa, were compared with those of tuatara, Sphenodon punctatus, the last living member of the Rhynchocephalian reptiles. We demonstrate that the lack of TCRg and TCRd transcripts in the skink are due to large deletions in the T. rugosa genome. We also show that tuataras are on a growing list of species, including sharks, frogs, birds, alligators, and platypus, that can use an atypical TCRd that appears to be a chimera of a TCR chain with an Ab-like Ag-binding domain. Tuatara represents the nearest living relative to squamates that retain gd T cells. The loss of gdTCR in the skink is due to genomic deletions that appear to be conserved in other squamates. The genes encoding the abTCR chains in the skink do not appear to have increased in complexity to compensate for the loss of gd T cells.enCopyright © 2022 by The American Association of Immunologists, Inc.T-LymphocytesAnimalsLizardsReceptors, Antigen, T-Cell, gamma-deltaGenomeT-LymphocytesAnimalsLizardsReceptors, Antigen, T-Cell, gamma-deltaGenomeJournal article10.4049/jimmunol.21011582022-05-24608044Bertozzi, T. [0000-0001-6665-3395]