Antibody responses of variable lymphocyte receptors in the lamprey

Alder, Matthew N.; Herrin, Brantley R.; Sadlonova, Andrea; Stockard, Cecil R.; Grizzle, William E.; Gartland, Lanier; Gartland, G. Larry; Boydston, Jeremy A.; Turnbough, Charles L.; Cooper, Max D.

doi:10.1038/ni1562

Cited by 151 publications

(162 citation statements)

References 41 publications

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“…In some ways the lamprey VLRA-and VLRC-expressing cells resemble the αβ and γδ T cells of jawed vertebrates, whereas the VLRB-bearing cells are more morphologically and functionally similar to B cells (12,14,16). Hagfish VLRC ("VLRA" in the old nomenclature) and VLRB are also expressed by two distinct lymphocyte populations (26), and the hagfish VLRB protein is secreted (27).…”

Section: Discussionmentioning

confidence: 99%

“…Lamprey VLRB-expressing cells can respond to immunization by undergoing lymphoblastoid transformation, clonal expansion, and secretion of their antigenspecific VLRB antibodies (9,14). VLRA-and VLRC-bearing cells also proliferate in response to antigen stimulation, but do not differentiate into antibody secreting cells; instead they maintain cell surface expression of their receptors, while increasing the expression of proinflammatory cytokines, macrophage migration inhibitory factor (MIF), and interleukin-17 (IL-17) (12).…”

mentioning

confidence: 99%

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Definition of a thirdVLRgene in hagfish

Das

Herrin

et al. 2013

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

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Jawless vertebrates (cyclostomes) have an alternative adaptive immune system in which lymphocytes somatically diversify their variable lymphocyte receptors (VLR) through recombinatorial use of leucine-rich repeat cassettes during VLR gene assembly. Three types of these anticipatory receptors in lampreys (VLRA, VLRB, and VLRC) are expressed by separate lymphocyte lineages. However, only two VLR genes (VLRA and VLRB) have been found in hagfish.Here we have identified a third hagfish VLR, which undergoes somatic assembly to generate sufficient diversity to encode a large repertoire of anticipatory receptors. Sequence analysis, structural comparison, and phylogenetic analysis indicate that the unique hagfish VLR is the counterpart of lamprey VLRA and the previously identified hagfish "VLRA" is the lamprey VLRC counterpart. The demonstration of three orthologous VLR genes in both lampreys and hagfish suggests that this anticipatory receptor system evolved in a common ancestor of the two cyclostome lineages around 480 Mya.adaptive immunity | molecular evolution | antigen receptor | agnatha

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Definition of a thirdVLRgene in hagfish

Das

Herrin

et al. 2013

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

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“…The processes controlling migration are likely to have evolved concomitantly with the differentiation of the thymus, in jawed vertebrates approximately 500 million years ago [19]. Indeed, in zebrafish, the migrational journey of individual hematopoietic precursors into the thymus can be visualized over more than 12 hours [20].…”

Section: Migration Of Hematopoietic Progenitors and Entry Into The Thmentioning

confidence: 99%

Concise Review: Hematopoietic Stem Cell Transplantation: Targeting the Thymus

2013

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Allogeneic hematopoietic stem cell (HSC) transplantation can cure patients suffering from diverse genetic and acquired diseases as well as cancers. Nevertheless, under conditions where T-cell reconstitution is critical, the entry of donor progenitors into the thymus remains a major bottleneck. It is assumed that following the intravenous injection of HSC, they first home to the BM. More committed progenitors can then be exported to the thymus in response to a myriad of signals regulating thymus seeding. Notably although, the thymus is not continually receptive to the import of hematopoietic progenitors. Furthermore, as stem cells with self-renewing capacity do not take up residence in the thymus under physiological conditions, the periodic colonization of the thymus is essential for the sustained differentiation of T lymphocytes. As such, we and others have invested significant efforts into exploring avenues that might foster a long-term thymus-autonomous differentiation. Here, we review strategic approaches that have resulted in long-term T-cell differentiation in immunodeficient (SCID) mice, even across histocompatibility barriers. These include the forced thymic entry of BM precursors by their direct intrathymic injection as well as the transplantation of neonatal thymi. The capacity of the thymus to support hematopoietic progenitors with renewal potential will hopefully promote the development of new therapeutic strategies aimed at enhancing T-cell differentiation in patients undergoing HSC transplantation.

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“…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%

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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Antibody responses of variable lymphocyte receptors in the lamprey

Cited by 151 publications

References 41 publications

Definition of a thirdVLRgene in hagfish

Definition of a thirdVLRgene in hagfish

Concise Review: Hematopoietic Stem Cell Transplantation: Targeting the Thymus

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

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