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Squamate reptiles are amongst the most successful terrestrial vertebrate lineages, with over 10,000 species across a broad range of ecosystems. Despite their success, squamates are also amongst the least studied lineages immunologically. Recently, a universal lack of γδ T cells in squamates due to deletions of the genes encoding the T cell receptor (TCR) γ and δ chains was discovered. Here, we begin to address how the loss of γδ T cells may have impacted the evolution of the squamate immune system. Using the skinkTiliqua rugosa, we found that squamates have not significantly increased the complexity of conventional T cell receptor beta (TCRβ orTRB) chain V regions compared to that of the nearest living squamate relative, the tuatara,Sphenodon punctatusor other amniotes. Our analyses include a putative new TCR locus. This novel locus contains V, D, and J gene segments that undergo V(D)J recombination, albeit with a limited number of gene segments in most squamate species. Based on conserved residues, the predicted protein chain would be expected to form a heterodimer with TCRα. This new TCR locus appears to be derived from an ancient duplication of theTRBlocus and is homologous to the recently described T cell receptor epsilon (TRE).TREis absent from the genomes of the tuatara and all Archosaurs examined and appears squamate specific.
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Comparison of Reptilian Genomes Reveals Deletions Associated with the Natural Loss of γδ T Cells in Squamates
Abstract T 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, αβ T cells and γδ 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 γδ T cells. In this study, we investigated the basis of the loss of the γδ 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 TCRγ and TCRδ 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 TCRδ 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 γδ T cells. The loss of γδTCR in the skink is due to genomic deletions that appear to be conserved in other squamates. The genes encoding the αβTCR chains in the skink do not appear to have increased in complexity to compensate for the loss of γδ T cells.
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- Award ID(s):
- 2103367
- PAR ID:
- 10571007
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- The Journal of Immunology
- Volume:
- 208
- Issue:
- 8
- ISSN:
- 0022-1767
- Format(s):
- Medium: X Size: p. 1960-1967
- Size(s):
- p. 1960-1967
- Sponsoring Org:
- National Science Foundation
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