Characteristics of the somatic hypermutation in the Camelus dromedarius T cell receptor gamma (TRG) and delta (TRD) variable domains

Ciccarese, Salvatrice; Vaccarelli, G.; Lefranc, Marie‐Paule; Tasco, Gianluca; Consiglio, Arianna; Casadio, Rita; Linguiti, Giovanna; Antonacci, Rachele

doi:10.1016/j.dci.2014.05.001

Cited by 32 publications

(37 citation statements)

References 38 publications

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“…Somatic hypermutations in T-cell receptor d and c genes increase the diversity repertoire of T-cells in dromedaries. They have not been identified in mammalian species so far and could enhance the acquirement of new antigenic specificity (Ciccarese et al 2014). On the contrary, a and b T-cells show a reduced repertoire with great sequence identity between orthologous genes in all three Old World camel species (Antonacci et al 2019).…”

Section: Immune Genesmentioning

confidence: 99%

Old World camels in a modern world – a balancing act between conservation and genetic improvement

Burger¹,

Ciani

Faye

2019

Animal Genetics

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Old World camels have served humans in cross-continental caravans, transporting people and goods, connecting different cultures and providing milk, meat, wool and draught since their domestication around 3000-6000 years ago. In a world of modern transport and fast connectivity, these beasts of burden seem to be out-dated. However, a growing demand for sustainable milk and meat production, especially in countries affected by climate change and increasing desertification, brings dromedaries (Camelus dromedarius) and Bactrian camels (Camelus bactrianus) back onstage and into the focus of animal breeders and scientists. In this review on the molecular genetics of these economically important species we give an overview about the evolutionary history, domestication and dispersal of Old World camels, whereas highlighting the need for conservation of wild two-humped camels (Camelus ferus) as an evolutionarily unique and highly endangered species. We provide cutting-edge information on the current molecular resources and on-going sequencing projects. We cannot emphasise enough the importance of balancing the need for improving camel production traits with maintaining the genetic diversity in two domestic species with specific physiological adaptation to a desert environment.

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Section: Immune Genesmentioning

confidence: 99%

Old World camels in a modern world – a balancing act between conservation and genetic improvement

Burger¹,

Ciani

Faye

2019

Animal Genetics

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“…Analyses included only sequences from peripheral lymphoid tissues, but mutation patterns are parallel to those of TCR γV and TCR αδV-TCR δC in our study. While overall mutation was fairly low (and did not favor G/C nucleotides), replacement mutation was biased toward AID hotspot motifs and resulted in greater length and diversity of CDR3 [31,32]. Crystalline structures of γδ TCR bound to nonclassical MHC demonstrate that MHC recognition occurs through direct contact by CDR3 of TCR delta [50], suggesting that cells with longer or more diverse CDR3 may be selected for survival.…”

Section: Discussionmentioning

confidence: 98%

“…Other examples exist to suggest that not only are Ig and TCR gene components interchangeable, but mechanisms of receptor diversification also are shared between B and T cells. In camelids, both gamma-and delta-V gene segments employ SHM to improve structural stability of receptors rather than antigen selection [31]. Analyses included only sequences from peripheral lymphoid tissues, but mutation patterns are parallel to those of TCR γV and TCR αδV-TCR δC in our study.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, T cells can exploit BCR diversification mechanisms like AID-catalyzed SHM to generate additional thymic diversity. Chen et al [29] presented definitive evidence that sandbar sharks utilize SHM to diversify gamma chain of γδ T cells, and camels employ SHM to diversify both TCR gamma and delta chains [29][30][31][32][33]. Additionally, nurse sharks utilize SHM for AID-catalyzed receptor salvaging to assist thymocytes through selection during thymic development [34].…”

Section: Introductionmentioning

confidence: 99%

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Nurse shark T‐cell receptors employ somatic hypermutation preferentially to alter alpha/delta variable segments associated with alpha constant region

et al. 2020

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In addition to canonical TCR and BCR, cartilaginous fish assemble noncanonical TCR that employ various B‐cell components. For example, shark T cells associate alpha (TCR‐α) or delta (TCR‐δ) constant (C) regions with Ig heavy chain (H) variable (V) segments or TCR‐associated Ig‐like V (TAILV) segments to form chimeric IgV‐TCR, and combine TCRδC with both Ig‐like and TCR‐like V segments to form the doubly rearranging NAR‐TCR. Activation‐induced (cytidine) deaminase‐catalyzed somatic hypermutation (SHM), typically used for B‐cell affinity maturation, also is used by TCR‐α during selection in the shark thymus presumably to salvage failing receptors. Here, we found that the use of SHM by nurse shark TCR varies depending on the particular V segment or C region used. First, SHM significantly alters alpha/delta V (TCRαδV) segments using TCR αC but not δC. Second, mutation to IgHV segments associated with TCR δC was reduced compared to mutation to TCR αδV associated with TCR αC. Mutation was present but limited in V segments of all other TCR chains including NAR‐TCR. Unexpectedly, we found preferential rearrangement of the noncanonical IgHV‐TCRδC over canonical TCR αδV‐TCRδC receptors. The differential use of SHM may reveal how activation‐induced (cytidine) deaminase targets V regions.

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“…With regard to the T-cell receptors (TCRs), it was found that although the germline repertoire of dromedaries appeared limited compared to that of other artiodactyls, extensive somatic hypermutation occurred on rearranged TRDV and TRGV genes to enhance their diversity (Antonacci et al, 2011;Ciccarese et al, 2014;Vaccarelli et al, 2012). This was quite unusual, as somatic hypermutation was only documented for IGs and not for TCRs in other mammals.…”

Section: Introductionmentioning

confidence: 99%

Chromosome‐level assembly of wild Bactrian camel genome reveals organization of immune gene loci

Liang

Wang

et al. 2020

Molecular Ecology Resources

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Camelids are characterized by their unique adaptive immune system that exhibits the generation of homodimeric heavy-chain immunoglobulins, somatic hypermutation of T-cell receptors, and low genetic diversity of major histocompatibility complex (MHC) genes. However, short-read assemblies are typically highly fragmented in these gene loci owing to their repetitive and polymorphic nature. Here, we constructed a chromosome-level assembly of wild Bactrian camel genome based on high-coverage long-read sequencing and chromatin interaction mapping. The assembly with a contig N50 of 5.37 Mb and a scaffold N50 of 76.03 Mb, represents the most contiguous camelid genome to date. The genomic organization of immunoglobulin heavy-chain locus was similar between the wild Bactrian camel and alpaca, and genes encoding for conventional and heavy-chain antibodies were intermixed. The organizations of two immunoglobulin light-chain loci and four T cell receptor loci were also fully deciphered using the new assembly. Additionally, the complete classical MHC region was resolved into a single contig. The high-quality assembly presented here provides an essential reference for future investigations examining the camelid immune system. K E Y W O R D S chromosome assembly, immunoglobin, long-read sequencing, major histocompatibility complex, T cell receptor, wild Bactrian camel | 771 MING et al.

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Characteristics of the somatic hypermutation in the Camelus dromedarius T cell receptor gamma (TRG) and delta (TRD) variable domains

Cited by 32 publications

References 38 publications

Old World camels in a modern world – a balancing act between conservation and genetic improvement

Old World camels in a modern world – a balancing act between conservation and genetic improvement

Nurse shark T‐cell receptors employ somatic hypermutation preferentially to alter alpha/delta variable segments associated with alpha constant region

Chromosome‐level assembly of wild Bactrian camel genome reveals organization of immune gene loci

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