Profiling the T Cell Receptor Alpha/Delta Locus in Salmonids

Abstract

In jawed vertebrates, two major T cell populations have been characterized. They are defined as α/β or γ/δ T cells, based on the expressed T cell receptor. Salmonids (family Salmonidae) include two key teleost species for aquaculture, rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar) which constitute important models for fish immunology and important targets for vaccine development. The growing interest to decipher the dynamics of adaptive immune responses against pathogens or vaccines has resulted in recent efforts to sequence the immunoglobulin (IG) or antibodies and T cell receptor (TR) repertoire in these species. In this context, establishing a comprehensive and coherent locus annotation is the fundamental basis for the analysis of high-throughput repertoire sequencing data. We therefore decided to revisit the description and annotation of TRA/TRD locus in Atlantic salmon and two strains of rainbow trout (Swanson and Arlee) using the now available high-quality genome assemblies. Phylogenetic analysis of functional TRA/TRD V genes from these three genomes led to the definition of 25 subgroups shared by both species, some with particular feature. A total of 128 TRAJ genes were identified in Salmo, the majority with a close counterpart in Oncorhynchus. Analysis of expressed TRA repertoire indicates that most TRAV gene subgroups are expressed at mucosal and systemic level. The present work on TRA/TRD locus annotation along with the analysis of TRA repertoire sequencing data show the feasibility and advantages of a common salmonid TRA/TRD nomenclature that allows an accurate annotation and analysis of high-throughput sequencing results, across salmonid T cell subsets.

Evolution of T cell receptor beta loci in salmonids

“…The TRBV3 subgroup was also expanded in Atlantic salmon which, along with TRBV11, -10 and -5, corresponded to the most expanded subgroups in this salmonid species (see Table 1). An analogous situation was previously described in rainbow trout and Atlantic salmon IGH and TRA/D loci, that present different numbers of variable genes in both species, which cluster in similar numbers of subgroups but with different distributions (14,15). Therefore, as described in other vertebrates, expansions of individual gene subgroups, rather than the emergence of novel sequences, seems to be the major mode of evolution of salmonid IG and TR variable genes (9,14,41,42).…”

Tetraploid Ancestry Provided Atlantic Salmon With Two Paralogue Functional T Cell Receptor Beta Regions Whereof One Is Completely Novel

“…The Atlantic salmon TRA/TRD region was shown to have an unprecedented 292 variable alpha/delta genes and 123 joining genes, which allows for a very diverse T cell receptor alpha chain (32,33). Adding the variable and joining genes in the duplicate TRB regions provides Atlantic salmon with the most diverse TRA/TRB opportunity of any vertebrate studied so far accommodating for a vast MHC-peptide diversity.…”

“…They discovered an unprecedented 292 variable TRA/TRD genes and 123 joining genes, exemplifying why these regions are very difficult to assemble. This region was recently revisited, expanding the understanding of Atlantic salmon TRA/TRD genes (33). Partial TRB regions containing D-J-C genes from catfish and rainbow trout were published in 1997 and 2003 (14,34).…”

IMGT®Homo sapiens IG and TR Loci, Gene Order, CNV and Haplotypes: New Concepts as a Paradigm for Jawed Vertebrates Genome Assemblies

“…The IMGT locus, gene order, CNV, haplotypes new concepts have been formalized for the comparison of genomic polymorphisms between different assemblies (chromosomes of individuals) in a given species for entries in databases. These concepts are also used for establishing the IMGT nomenclature of the IG and TR genes of new loci of genome assemblies of new species, differences in gene content in haplotypes, from fish to humans, as recently demonstrated, between strains, for the Salmonid IGH and TRA/TRD loci [139,140].…”

“…For an easier comparison between loci of different species, and/or between loci of different genomes assemblies (or of different haplotypes, including CNV), the IDENTIFICATION axiom has been enriched by the implementation of 'IMGT locus ID' and 'IMGT/LIGM-DB locus reference sequence (ID)' (Figure 3). Recent examples of veterinary IG and TR loci from genome assemblies, analyzed by scientists using gene and allele names validated by the IUIS NOM IMGT-NC [114], include: dog (Canis lupus familiaris) [134], the first veterinary species with the seven loci identified, cat (Felis catus) TR loci [135], rabbit (Oryctolagus cuniculus) TRA locus [136], dolphin (Tursiops truncatus) [137], Salmonid including salmon (Salmo salar) and trout (Oncorhynchus mykiss) IGH duplicated loci [138,139] and TRA/TRD locus [140]. These examples of different species and loci have been key elements in the setting of the submission criteria and steps of the now well established IUIS NOM IMGT-NC Reports [114].…”