Variable lymphocyte receptors in hagfish

Pancer, Zeev; Saha, Nil Ratan; Kasamatsu, Jun; Suzuki, Takashi; Amemiya, Chris T.; Kasahara, Masanori; Cooper, Max D.

doi:10.1073/pnas.0503792102

Cited by 202 publications

(171 citation statements)

References 23 publications

Supporting

Mentioning

164

Contrasting

Unclassified

Order By: Relevance

“…The germline-diversified V domains in NITRs are an example of an adaptive immune feature in an innate immune receptor 73,74 , whereas germline joining of immunoglobulin-gene clusters in cartilaginous fish is an example of an innate immune feature in an adaptive immune receptor 18 . The Dscam variants in insects 10 , the FREPs in snails 8,126 , the VLRs in the jawless vertebrates lampreys 9 and hagfish 99 , and the VCBPs in the protochordate amphioxus 7,113 all share certain fundamental characteristics with the adaptive antigen-binding immune receptors of jawed vertebrates.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Reconstructing immune phylogeny: new perspectives

2005

View full text Add to dashboard Cite

Numerous studies of the mammalian immune system have begun to uncover profound interrelationships, as well as fundamental differences, between the adaptive and innate systems of immune recognition. Coincident with these investigations, the increasing experimental accessibility of non-mammalian jawed vertebrates, jawless vertebrates, protochordates and invertebrates has provided intriguing new information regarding the likely patterns of emergence of immune-related molecules during metazoan phylogeny, as well as the evolution of alternative mechanisms for receptor diversification. Such findings blur traditional distinctions between adaptive and innate immunity and emphasize that, throughout evolution, the immune system has used a remarkably extensive variety of solutions to meet fundamentally similar requirements for host protection.The evolutionary development of the METAZOANS was associated with the diversification of a wide range of specialized cell-surface molecules that mediate key metabolic processes, as well as provide crucial contact interfaces and carry out a broad range of other essential functions. It is not unexpected that some of these molecules also came to function as barriers to pathogenic invasion and, in doing so, began to carry out dedicated innate immune protective functions. Whereas the simplest form of protection, barrier formation, is essentially mechanical in nature, relentless pressure from genetic variation in pathogens probably drove the evolution of such innate immune protective molecules towards diversification and, in parallel, towards integration of signalling pathways to regulate cellular responses to external stimulation. However, despite the sophistication that such innate immune mediators achieved over time, their biological complexity, by definition, would be limited by genome space, so with increasing complexity of body plan and/or increasing pathogen sophistication, they could be overwhelmed. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMore than 500 million years ago, a TRANSPOSITION event, probably involving a recombinationactivating gene (RAG)-bearing element, might have given rise to the predecessors of the rearranging antigen-binding receptors of the jawed vertebrates, which encompass the vertebrate radiations that extend from the cartilaginous fish through to humans. This is considered the defining point in the emergence of RAG-mediated (conventional) adaptive immunity 1,2 , which has evolved to create a mechanism for deriving almost limitless variation from very few genes. Studies in traditional and non-traditional animal models, such as sharks, bony fish and birds, have brought this event and its ramifications for host defence into sharper focus. We can now predict much about how these rearranging antigenbinding receptors probably arose, what alternative pathways of immune-receptor gene evolution have occurred, what relationships exist between B-and T-cell-mediated immunity and natural killer (NK)-cell function, how complex immune ...

show abstract

Section: Discussionmentioning

confidence: 99%

“…Single-cell PCR is consistent with haplotypic exclusion, a characteristic of lymphocyte-mediated immunity and a central feature of clonal selection in RAG-mediated adaptive immunity. VLRs that undergo similar genetic rearrangement have also been characterized in hagfish 99 .…”

Section: Anticipatory Immunity In Jawless Vertebratesmentioning

confidence: 99%

Reconstructing immune phylogeny: new perspectives

2005

View full text Add to dashboard Cite

show abstract

“…is comprised of clonally diverse lymphocytes that express variable lymphocyte receptors (VLRs) created by the combinatorial assembly of leucine-rich repeat (LRR) gene segments rather than the Ig V, D, and J gene segments used by jawed vertebrates (gnathostomes) (1,2). Two VLR genes, VLR-A and VLR-B, have been identified in both lamprey and hagfish (1)(2)(3).…”

Section: T He Adaptive Immune System In Jawless Vertebrates (Agnathans)mentioning

confidence: 99%

Section: T He Adaptive Immune System In Jawless Vertebrates (Agnathans)mentioning

confidence: 99%

“…Two VLR genes, VLR-A and VLR-B, have been identified in both lamprey and hagfish (1)(2)(3). The germline VLR genes are incomplete in that they have coding regions only for the invariant N-terminal and C-terminal sequences, which are separated by intervening sequences, lacking canonical splice sites (1,2). During development of lymphocyte lineage cells, components of the flanking LRR modular units are sequentially inserted into the incomplete VLR gene with a concomitant deletion of the intervening sequences (4,5).…”

Section: T He Adaptive Immune System In Jawless Vertebrates (Agnathans)mentioning

confidence: 99%

See 1 more Smart Citation

Structure and specificity of lamprey monoclonal antibodies

Herrin

Alder

Roux

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

142

168

View full text Add to dashboard Cite

Adaptive immunity in jawless vertebrates (lamprey and hagfish) is mediated by lymphocytes that undergo combinatorial assembly of leucine-rich repeat (LRR) gene segments to create a diverse repertoire of variable lymphocyte receptor (VLR) genes. Immunization with particulate antigens induces VLR-B-bearing lymphocytes to secrete antigen-specific VLR-B antibodies. Here, we describe the production of recombinant VLR-B antibodies specific for BclA, a major coat protein of Bacillus anthracis spores. The recombinant VLR-B antibodies possess 8 -10 uniform subunits that collectively bind antigen with high avidity. Sequence analysis, mutagenesis, and modeling studies show that antigen binding involves residues in the ␤-sheets lining the VLR-B concave surface. EM visualization reveals tetrameric and pentameric molecules having a central core and highly flexible pairs of stalk-region ''arms'' with antigenbinding ''hands.'' Remarkable antigen-binding specificity, avidity, and stability predict that these unusual LRR-based monoclonal antibodies will find many biomedical uses.antigen-binding site ͉ leucine-rich repeat ͉ variable lymphocyte receptor

show abstract

Immunology of Fish

Fletcher¹,

Secombes²

2010

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Innate immunity provides some form of defence against pathogens in all multicellular organisms but with cartilaginous and bony fish, although the lowest group of jawed vertebrates, the addition of a classic adaptive immune response becomes apparent. This provides the refinements of specificity for antigen recognition and memory. The T‐ and B lymphocytes are the effector leucocytes, acquiring their antigen‐specific receptors (immunoglobulin for B cells and T‐cell receptor for T cells) in the anterior kidney (bone marrow being absent) and thymus. The B cells are responsible for the production of antibodies that function as different immunoglobulin classes, whereas subsets of T lymphocytes are capable of killing target cells or helping with B‐ and other T‐cell functions. Knowledge of these mechanisms is important for the use and design of vaccines, now so essential for the aquaculture industry, whereas studies of fish immunology contribute to the understanding of the evolution of adaptive immunity. Key concepts: Fish possess innate and adaptive immune responses, with classical adaptive immunity present only in jawed vertebrates. Adaptive immunity allows memory of prior exposure to foreign molecules (antigens), so that on subsequent contact protective mechanisms are more rapidly mobilized: the basis of vaccination. Lymphocytes mediate adaptive immunity and have surface receptors that recognize antigens, initiating the production of circulating antibodies and the activation of cell‐mediated responses. The functions of the immune system are similar in fish and mammals although there are differences due to the aquatic physiology and ectothermic nature of fish that provide evolutionary interest. Leucocyte–antigen interactions take place in immune sites, such as the kidneys, spleen, gills and intestine. Bone marrow and lymph nodes are lacking. Knowledge of fish immunology is proving essential for the development of vaccines for the expanding aquaculture industry.

show abstract

Variable lymphocyte receptors in hagfish

Cited by 202 publications

References 23 publications

Reconstructing immune phylogeny: new perspectives

Reconstructing immune phylogeny: new perspectives

Structure and specificity of lamprey monoclonal antibodies

Immunology of Fish

Contact Info

Product

Resources

About