Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen

Velikovsky, Carlos A.; Deng, Lu; Tasumi, Satoshi; Iyer, Lakshminarayan M.; Kerzic, Melissa C.; Aravind, L.; Pancer, Zeev; Mariuzza, Roy A.

doi:10.1038/nsmb.1619

Cited by 106 publications

(164 citation statements)

References 38 publications

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“…Although LRRNT does not contact ligand in the two VLRBantigen complexes (3,5), LRRNT of VLRA.R2.1 engages HEL through Gln21, which forms two side-chain-side-chain hydrogen bonds with HEL Arg61 (Fig. 3A and Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…VLRA.R2.1 adopts a horseshoe- shaped solenoid fold similar to that of VLRBs ( Fig. 1 A and B) (3)(4)(5). The structure comprises an N-terminal LRR capping module (LRRNT), six LRR modules (LRR1, LRRV1 through LRRV4, and LRRVe), a truncated LRR designated the connecting peptide (CP), and a C-terminal LRR capping module (LRRCT).…”

Section: Resultsmentioning

confidence: 99%

“…Thus, VLRB lymphocytes respond to antigenic stimulation by proliferating and differentiating into plasmacytes that secrete VLRBs specific for native antigens. Like IgM antibodies, VLRBs overcome their weak monomeric affinities (micromolar K D s) by forming high-avidity multimers (5,11). By contrast, VLRA lymphocytes do not secrete their receptors following antigen activation.…”

mentioning

confidence: 99%

“…Recently, crystal structures of VLRBs bound to H-antigen trisaccharide and hen egg white lysozyme (HEL) were reported (3,5), showing how VLRB lymphocytes bind carbohydrate and protein antigens. By contrast, the mode of antigen recognition by VLRA lymphocytes is unknown.…”

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.…”

mentioning

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: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

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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In‐Film Bioprocessing and Immunoanalysis with Electroaddressable Stimuli‐Responsive Polysaccharides

Yang

Kim

Liu

et al. 2010

Adv Funct Materials

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Advances in thin‐film fabrication are integral to enhancing the power of microelectronics while fabrication methods that allow the integration of biological molecules are enabling advances in bioelectronics. A thin‐film‐fabrication method that further extends the integration of biology with microelectronics by allowing living biological systems to be assembled, cultured, and analyzed on‐chip with the aid of localized electrical signals is described. Specifically, the blending of two stimuli‐responsive film‐forming polysaccharides for electroaddressing is reported. The first, alginate, can electrodeposit by undergoing a localized sol–gel transition in response to electrode‐imposed anodic signals. The second, agarose, can be co‐deposited with alginate and forms a gel upon a temperature reduction. Electrodeposition of this dual polysaccharide network is observed to be a simple, rapid, and spatially selective means for assembly. The bioprocessing capabilities are examined by co‐depositing a yeast clone engineered to display a variable lymphocyte receptor protein on the cell surface. Results demonstrate the in‐film expansion and induction of this cell population. Analysis of the cells' surface proteins is achieved by the electrophoretic delivery of immunoreagents into the film. These results demonstrate a simple and benign means to electroaddress hydrogel films for in‐film bioprocessing and immunoanalysis.

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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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Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen

Cited by 106 publications

References 38 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

In‐Film Bioprocessing and Immunoanalysis with Electroaddressable Stimuli‐Responsive Polysaccharides

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

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