Diversity and Function of Adaptive Immune Receptors in a Jawless Vertebrate

Alder, Matthew N.; Rogozin, Igor B.; Iyer, Lakshminarayan M.; Glazko, Galina V.; Cooper, Max D.; Pancer, Zeev

doi:10.1126/science.1119420

Cited by 289 publications

(307 citation statements)

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“…All VLR sequences used here were derived from previous studies (1,2,9). Protein sequence searches were performed using the BLASTPGP and PSI-BLAST programs (31), with a profile threshold of 0.01.…”

Section: Methodsmentioning

confidence: 99%

“…There are two types of VLRs, denoted "A" and "B," which are expressed by mutually exclusive lymphocyte populations through monoallelic assembly of VLRA or VLRB genes (1,2,7). VLRB lymphocytes resemble the B cells of jawed vertebrates, whereas VLRA lymphocytes are surprisingly similar to T cells (10).…”

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confidence: 99%

“…Like antibodies and TCRs, VLRs are generated in lymphocytes by DNA recombination. However, antibodies and TCRs are assembled from V, D, and J gene segments, and VLRs are assembled from multiple LRR-encoding cassettes selected from several hundred that flank each germline VLR gene (2,6,7). This process can generate a vast repertoire of receptors, estimated to comprise more than 10 14 unique VLRs, which is sufficiently diverse to recognize most, if not all, pathogens (7)(8)(9).…”

mentioning

confidence: 99%

“…In jawless vertebrates, adaptive immunity is mediated by antigen receptors that are fundamentally different from those of jawed vertebrates. Antibodies and TCRs are composed of Ig domains, but the variable lymphocyte receptors (VLRs) of jawless fish (lamprey and hagfish) consist of leucine-rich repeat (LRR) modules (1)(2)(3)(4)(5). Like antibodies and TCRs, VLRs are generated in lymphocytes by DNA recombination.…”

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confidence: 99%

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A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey

Deng

Velikovsky

et al. 2010

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

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Adaptive immunity in jawless vertebrates is mediated by leucine-rich repeat proteins called "variable lymphocyte receptors" (VLRs). Two types of VLR (A and B) are expressed by mutually exclusive lymphocyte populations in lamprey. VLRB lymphocytes resemble the B cells of jawed vertebrates; VLRA lymphocytes are similar to T cells. We determined the structure of a high-affinity VLRA isolated from lamprey immunized with hen egg white lysozyme (HEL) in unbound and antigen-bound forms. The VLRA-HEL complex demonstrates that certain VLRAs, like γδ T-cell receptors (TCRs) but unlike αβ TCRs, can recognize antigens directly, without a requirement for processing or antigen-presenting molecules. Thus, these VLRAs feature the nanomolar affinities of antibodies, the direct recognition of unprocessed antigens of both antibodies and γδ TCRs, and the exclusive expression on the lymphocyte surface that is unique to αβ and γδ TCRs.crystal structure | T-cell receptor | variable lymphocyte receptor | evolution | antigen binding

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey

Deng

Velikovsky

et al. 2010

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

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“…Il y a environ 470 millions d'années, alors que certains rudiments de la diversité immunitaire résultant d'une simple conversion génique existaient déjà chez les premiers vertébrés -les poissons dépourvus de mâchoires (Agnathes) comme la lamproie - [3] l'immunité adaptative s'est développée avec l'apparition des poissons cartilagineux (comme le requin ou la raie). L'immunité adaptative se caractérise par l'acquisition d'une machinerie enzymatique (les recombinases RAG1 et RAG2), spécialisée dans la recombinaison aléatoire de segments de gènes au sein des cellules somatiques lymphoïdes.…”

Section: Introductionunclassified

Les cibles hormonales de la réponse auto-immune

Geenen

2008

Annales d'Endocrinologie

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors

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Evolution of adaptive immunity: Implications of a third lymphocyte lineage in lampreys

Kishishita

Nagawa

2013

BioEssays

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An alternative antigen receptor, named the variable lymphocyte receptor (VLR), was first identified in lampreys in 2004. Since then, the mechanism of VLR diversification via somatic gene assembly and the function of VLR-expressing lymphocytes have been the subject of much research. VLRs comprise leucine-rich repeat (LRR) motifs and are found only in the most phylogenetically distant vertebrates from mammals, lampreys, and hagfish. Previous reports showed that VLRA and VLRB are reciprocally expressed by lymphocytes that resemble T- and B cells; however, more recent reports show that another VLR, VLRC, is expressed on a third lymphocyte lineage, which may be equivalent to γδ T cells. The existence of three major lymphocyte lineages - one B-cell-like and two T-cell-like - and their development in lampreys, parallels the mammalian adaptive immune system. This suggests that these three cell lineages were present in the common vertebrate ancestor approximately 500 million years ago.

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Diversity and Function of Adaptive Immune Receptors in a Jawless Vertebrate

Cited by 289 publications

References 21 publications

A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey

A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey

Les cibles hormonales de la réponse auto-immune

Evolution of adaptive immunity: Implications of a third lymphocyte lineage in lampreys

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