Abstract
BackgroundThe domestic cat (Felis catus) is an important companion animal and is used as a large animal model for human disease. However, the comprehensive study of adaptive immunity in this species is hampered by the lack of data on lymphocyte antigen receptor genes and usage. The objectives of this study were to annotate the feline T cell receptor (TR) loci and to characterize the expressed repertoire in lymphoid organs of normal cats using high-throughput sequencing.ResultsThe Felis catus TRG locus contains 30 genes: 12 TRGV, 12 TRGJ and 6 TRGC, the TRB locus contains 48 genes: 33 TRBV, 2 TRBD, 11 TRBJ, 2 TRBC, the TRD locus contains 19 genes: 11 TRDV, 2 TRDD, 5 TRDJ, 1 TRDC, and the TRA locus contains 127 genes: 62 TRAV, 64 TRAJ, 1 TRAC. Functional feline V genes form monophyletic clades with their orthologs, and clustering of multimember subgroups frequently occurs in V genes located at the 5′ end of TR loci. Recombination signal (RS) sequences of the heptamer and nonamer of functional V and J genes are highly conserved. Analysis of the TRG expressed repertoire showed preferential intra-cassette over inter-cassette rearrangements and dominant usage of the TRGV2–1 and TRGJ1–2 genes. The usage of TRBV genes showed minor bias but TRBJ genes of the second J-C-cluster were more commonly rearranged than TRBJ genes of the first cluster. The TRA/TRD V genes almost exclusively rearranged to J genes within their locus. The TRAV/TRAJ gene usage was relatively balanced while the TRD repertoire was dominated by TRDJ3.ConclusionsThis is the first description of all TR loci in the cat. The genomic organization of feline TR loci was similar to that of previously described jawed vertebrates (gnathostomata) and is compatible with the birth-and-death model of evolution. The large-scale characterization of feline TR genes provides comprehensive baseline data on immune repertoires in healthy cats and will facilitate the development of improved reagents for the diagnosis of lymphoproliferative diseases in cats. In addition, these data might benefit studies using cats as a large animal model for human disease.
Highlights
The domestic cat (Felis catus) is an important companion animal and is used as a large animal model for human disease
The T cell receptor (TR) protein chains are encoded by four TR loci, TR beta (TRB), TR gamma (TRG) and the intertwined TR alpha (TRA) and TR delta (TRD) loci [1]
The feline TRGV genes belong to 6 subgroups, two of them having 4 members (TRGV2 with 4 F, TRGV5 with 1 F and 3P) and the four other with a single member each; subgroup TRGV7 being the only one with a functional gene, subgroup TRGV6 containing two STOP-CODON in the V-REGION, TRGVA and TRGVB that are degenerate pseudogenes
Summary
The domestic cat (Felis catus) is an important companion animal and is used as a large animal model for human disease. The T cell receptor (TR) protein chains are encoded by four TR loci, TR beta (TRB), TR gamma (TRG) and the intertwined TR alpha (TRA) and TR delta (TRD) loci [1]. The complete TRB and TRD chains are Radtanakatikanon et al BMC Genomics (2020) 21:20 flanking the V, D, and J genes [6]. The lymphocyte specific endonuclease recombinase activating genes (composed of RAG1 and RAG2) initiate non-homologous end-joining (NHEJ) by breaking double-stranded DNA between the coding regions and their adjacent RS. Junctional diversity is introduced by an exonuclease which removes nucleotides at the 3′ or 5′ end of the coding region of the genes which rearrange and by the templateindependent DNA polymerase called terminal deoxynucleotidyl transferase (TdT) which randomly adds nucleotides not encoded in the germline genomes and creates the Ndiversity regions [7]. The resulting hypervariable region is referred to as the complementarity determining region 3 (CDR3), which forms, with the germline encoded CDR1 and CDR2, the antigen-binding site and determines the specificity of the antigen receptor
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