Overview of the Germline and Expressed Repertoires of the TRB Genes in Sus scrofa

Abstract

The α/β T cell receptor (TR) is a complex heterodimer that recognizes antigenic peptides and binds to major histocompatibility complex (MH) molecules. Both α and β chains are encoded by different genes localized on two distinct chromosomal loci: TRA and TRB. The present study employed the recent release of the swine genome assembly to define the genomic organization of the TRB locus. According to the sequencing data, the pig TRB locus spans approximately 400 kb of genomic DNA and consists of 38 TRBV genes belonging to 24 subgroups located upstream of three in tandem TRBD-J-C clusters, which are followed by a TRBV gene in an inverted transcriptional orientation. Comparative analysis confirms that the general organization of the TRB locus is similar among mammalian species, but the number of germline TRBV genes varies greatly even between species belonging to the same order, determining the diversity and specificity of the immune response. However, sequence analysis of the TRB locus also suggests the presence of blocks of conserved homology in the genomic region across mammals. Furthermore, by analysing a public cDNA collection, we identified the usage pattern of the TRBV, TRBD, and TRBJ genes in the adult pig TRB repertoire, and we noted that the expressed TRBV repertoire seems to be broader and more diverse than the germline repertoire, in line with the presence of a high level of TRBV gene polymorphisms. Because the nucleotide differences seems to be principally concentrated in the CDR2 region, it is reasonable to presume that most T cell β-chain diversity can be related to polymorphisms in pig MH molecules. Domestic pigs represent a valuable animal model as they are even more anatomically, genetically and physiologically similar to humans than are mice. Therefore, present knowledge on the genomic organization of the pig TRB locus allows the collection of increased information on the basic aspects of the porcine immune system and contributes to filling the gaps left by rodent models.

The expansion of the TRB and TRG genes in domestic goats (Capra hircus) is characteristic of the ruminant species

“…(dromedary TRB locus contig as characterized by [14][15]; NC_010460 (pig TRB locus contig as characterized by [16]); and NC_030811.1 (this work) (goat TRB locus contig). We combined the nucleotide sequences of the V-REGION of the goat TRBV genes with the corresponding gene sequences of sheep, pig and dromedary.…”

“…In human, mouse, and several other mammals (https://www.imgt.org/IMGTrepertoire/: Homo sapiens, Mus musculus; [7,8,9,10,11]), two TRBD-J-C clusters have been identi ed. In contrast, in the artiodactyl lineage [12,13,14,15,16,17], a duplication event within the 3′ end of the TRB locus has led to the generation of a third TRBD-J-C cluster. Moreover, ruminants appear to have an increased number of genes in the TRBV gene pool, which is the largest in cattle (134 TRBV genes) [13], and sheep (94 TRBV genes) [11] and resulted from massive expansion of mainly two TRBV gene subgroups.…”

The Expansion of the TRB and TRG Genes in Domestic Goats (Capra hircus) is Characteristic of the Ruminant Species

“…We identi ed and annotated all TRB genes using the sheep sequence as a reference [11][12]. The general structural organization of the goat TRB locus is conserved with respect to the other artiodactyl species [11][12][13][14][16][17], with a library of TRBV genes positioned at the 5' end of three D-J-C clusters, that is followed by a single TRBV gene located at the 3' end in an inverted transcriptional orientation ( Fig. 1).…”

“…The difference of sixteen nucleotides between them results in seven AA changes, with six clustered in the extracellular region (C-domain) and one in the cytoplasmic region (Additional le 9: Figure S3C). As in sheep, the C-domain encoded by exon (EX) 1 is 130 AA in length due to the identical length of the FG loop compared to the other artiodactyl species [14,16]. The C region also comprises a connecting region of 21 AA (encoded by EX2 and the 5' part of EX3) with a cysteine involved in interchain disulphide binding, a transmembrane region of 21 AA (encoded by the 3' part of EX3 and the rst codon of EX4) and a cytoplasmic region of 5 AA (encoded by EX4).…”

“…In human, mouse, and several other mammals (https://www.imgt.org/IMGTrepertoire/: Homo sapiens, Mus musculus; [7,8,9,10,11]), two TRBD-J-C clusters have been identi ed. In contrast, in the artiodactyl lineage [12,13,14,15,16,17], a duplication event within the 3′ end of the TRB locus has led to the generation of a third TRBD-J-C cluster.…”