Lost structural and functional inter-relationships between Ig and TCR loci in mammals revealed in sharks

Ott, Jeannine A.; Ohta, Yuko; Flajnik, Martin F.; Criscitiello, Michael F.

doi:10.1007/s00251-020-01183-5

Cited by 12 publications

(5 citation statements)

References 139 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In comparing optimality and mutability, robust inverse relationships were observed for IGHV, IGKV, and IGLV, indicating that the more mutable the allele, the less codon-optimal. Interestingly, similar observations were made for TRAV and TRBV; despite being non-mutative in humans, both classes of receptor may have evolved from an AIDtargeted mutating precursor [41][42][43] . The correlation within immunoglobulin V genes was maintained when CSC N , CUFs, and (in the case of light chains) CAI values were instead used to quantify optimality (Figure 2a).…”

Section: Immunoglobulin V Genes Exhibit An Inverse Relationship Betwe...supporting

confidence: 65%

Mutability and hypermutation antagonize immunoglobulin codon optimality

McGrath,

Park,

Troxell

et al. 2024

Preprint

View full text Add to dashboard Cite

The efficacy of polyclonal antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation (SHM). These processes arose in early jawed vertebrates; however, little is known about how immunoglobulin diversity, mutability, and hypermutation have evolved in tandem with another more ubiquitous feature of protein-coding DNA - codon optimality. Here, we explore these relationships through analysis of germline IG genes, natural V(D)J repertoires, serum VH usage, and monoclonal antibody (mAb) expression, each through the lens of multiple optimality metrics. Strikingly, proteomic serum IgG sequencing showed that germline IGHV codon optimality positively correlated with VH representation after influenza vaccination, and in vitro, codon deoptimization of mAbs with synonymous amino acid sequences caused consistent expression loss. Germline V genes exhibit a range of codon optimality that is maintained by functionality, and inversely related to mutability. SHM caused a load-dependent deoptimization of IGH VDJ repertoires within human tonsils, bone marrow, and lymph nodes (including SARS-CoV-2-specific clones from mRNA vaccinees), influenza-infected mice, and zebrafish. Comparison of natural mutation profiles to true random suggests the presence of selective pressures that constrain deoptimization. These findings shed light on immunoglobulin evolution, providing unanticipated insights into the antagonistic relationship between variable region diversification, codon optimality, and antibody secretion; ultimately, the need for diversity takes precedence over that for the most efficient expression of the antibody repertoire.

show abstract

Section: Immunoglobulin V Genes Exhibit An Inverse Relationship Betwe...supporting

confidence: 65%

Mutability and hypermutation antagonize immunoglobulin codon optimality

McGrath,

Park,

Troxell

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…The proposed TRA/TRD locus annotation reflects the phylogenetic relationships between genes from Oncorhynchus (rainbow trout) and Salmo (Atlantic salmon). This resource will facilitate understanding diversification mechanisms, and should contribute to assess somatic hypermutation of TR sequences, a process recently reported ( 75 ). Hypermutation has been observed in dromedary ( Camelus dromedarius ) TRG/TRD ( 3 , 76 , 77 ), in sandbar shark ( Carcharhinus plumbeus ) TRG ( 78 , 79 ), in nurse shark ( Ginglymostoma cirratum ) TRA ( 75 , 80 ) and in the teleost ballan wrasse ( Labrus bergylta ) TRA ( 81 ).…”

Section: Discussionmentioning

confidence: 94%

Profiling the T Cell Receptor Alpha/Delta Locus in Salmonids

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

“…The final noncanonical TCR form incorporates unique IgH-like V segments present within the TCRad locus that, so far, have been found in all jawed vertebrate lineages except teleost fishes and placental mammals (reviewed in Ref. 59). Interestingly, a few studies have now shown AID-mediated somatic mutation of TCR V regions, as well as Ig genes, in several species from across jawed vertebrate phylogeny (6062).…”

Section: Jawed Vertebrate Adaptive Immune Receptors Exhibit Lineage-specific Noveltiesmentioning

confidence: 99%

Immunological Diversity Is a Cornerstone of Organismal Defense and Allorecognition across Metazoa

Buckley

Dooley

2022

The Journal of Immunology

View full text Add to dashboard Cite

The ongoing arms race between hosts and microbes has fueled the evolution of novel strategies for diversifying the molecules involved in immune responses. Characterization of immune systems from an ever-broadening phylogenetic range of organisms reveals that there are many mechanisms by which this diversity can be generated and maintained. Diversification strategies operate at the level of populations, genomes, genes, and even individual transcripts. Lineage-specific innovations have been cataloged within the immune systems of both invertebrates and vertebrates. Furthermore, somatic diversification of immune receptor genes has now been described in jawless vertebrates and some invertebrate species. In addition to pathogen detection, immunological diversity plays important roles in several distinct allorecognition systems. In this Brief Review, we highlight some of the evolutionary innovations employed by a variety of metazoan species to generate the molecular diversity required to detect a vast array of molecules in the context of both immune response and self/nonself-recognition.

show abstract

Lost structural and functional inter-relationships between Ig and TCR loci in mammals revealed in sharks

Cited by 12 publications

References 139 publications

Mutability and hypermutation antagonize immunoglobulin codon optimality

Mutability and hypermutation antagonize immunoglobulin codon optimality

Profiling the T Cell Receptor Alpha/Delta Locus in Salmonids

Immunological Diversity Is a Cornerstone of Organismal Defense and Allorecognition across Metazoa

Contact Info

Product

Resources

About