Protochordate allorecognition is controlled by a MHC-like gene system

Scofield, Virginia L.; Schlumpberger, J. M.; West, Lyndsay; Weissman, Irving L.

doi:10.1038/295499a0

Cited by 405 publications

(257 citation statements)

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“…The apparent absence of MHC class I or class II molecules in species that occupy positions below the phylogenetic level of jawed vertebrates 38 confounds efforts to assign the ancestral form of the conventional adaptive immune receptors as being either BCR-or TCR-like and might present an intractable problem. Notably, despite the apparent absence of MHC molecules, Botryllus schlosseri (a colonial protochordate) 142 and Hydractinia species (cnidarians; which are invertebrates) 143,144 show HISTOCOMPATIBILITY REACTIONS (that is, allotransplantation reactions) through a process known as fusibility, which protects the germline by inhibiting chimerism and/or parasitism 145 . Fusibility is determined by a single Mendelian trait and, in Botryllus schlosseri 146 , is mediated by highly polymorphic cell-surface receptors that contain immunoglobulin-superfamily and epidermal-growth-factor domains that are encoded at a single locus 147 .…”

Section: Box 1 Alternative Mediators Of Histocompatibilitymentioning

confidence: 99%

Reconstructing immune phylogeny: new perspectives

2005

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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 ...

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Section: Box 1 Alternative Mediators Of Histocompatibilitymentioning

confidence: 99%

Reconstructing immune phylogeny: new perspectives

2005

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“…We showed that this primitive immune response was controlled by a single highly polymorphic locus or haplotype (177). The rules of fusion or rejection follow those of NK recognition of self, wherein sharing a single allele halts the effector immune reactions that occur between zooids or colonies that do not share an allele at the locus (177)(178)(179)(180).…”

Section: Cancer Stem Cells and The Therapeutics That Come From Them: mentioning

confidence: 99%

“…Rejecting colonies, however, did not became somatic or germline chimeras (181). Therefore we proposed that clonal progression of stem cell competitive behaviors was a natural evolution, that germline stem cells were units of natural selection, and that the polymorphic histocompatibility in this species limited predatory germline stem cells from invading anything but histocompatible kin, insofar as the histocompatibility locus had hundreds of alleles, and the probability that anything but kin would share an allele was very low (166,177). We proposed that the ultimate extension of clonal stem cell competitions was cancer and that this limitation of fusion to kin protected both the diversity and the viability of the species (161,183,184).…”

Section: Cancer Stem Cells and The Therapeutics That Come From Them: mentioning

confidence: 99%

How One Thing Led to Another

Weissman

2016

Annu. Rev. Immunol.

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I started research in high school, experimenting on immunological tolerance to transplantation antigens. This led to studies of the thymus as the site of maturation of T cells, which led to the discovery, isolation, and clinical transplantation of purified hematopoietic stem cells (HSCs). The induction of immune tolerance with HSCs has led to isolation of other tissue-specific stem cells for regenerative medicine. Our studies of circulating competing germline stem cells in colonial protochordates led us to document competing HSCs. In human acute myelogenous leukemia we showed that all preleukemic mutations occur in HSCs, and determined their order; the final mutations occur in a multipotent progenitor derived from the preleukemic HSC clone. With these, we discovered that CD47 is an upregulated gene in all human cancers and is a “don't eat me” signal; blocking it with antibodies leads to cancer cell phagocytosis. CD47 is the first known gene common to all cancers and is a target for cancer immunotherapy.

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“…Self-non-self discrimination and other recognition systems, controlled by a highly polymorphic locus, are found in a wide range of organisms. Allorecognition is widespread and is integral to the animal immune response (Hughes 2002 ), fusion histocompatibility in lower animals (Scofi eld et al 1982 ;De Tomaso et al 2005 ;Nyholm et al 2006 ), vegetative incompatibility in fungi (Glass et al 2000 ), disease resistance in plants (Dangl and Jones 2001 ), and selfincompatibility (SI) systems found in many fl owering plants (Takayama and Isogai 2005 ;Franklin-Tong 2008 ). Parallels between nonanalogous recognition systems were recognized, and their importance appreciated, many years ago (Burnet 1971 ), long before the molecular basis of these systems were elucidated.…”

Section: Introductionmentioning

confidence: 99%

Papaver rhoeas S-Determinants and the Signaling Networks They Trigger

Franklin‐Tong

2014

Sexual Reproduction in Animals and Plants

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Higher plants use specifi c interactions between pollen and pistil to achieve pollination. Self-incompatibility (SI) is an important mechanism used by many species to prevent inbreeding. It is controlled by a multi-allelic S locus. "Self" (incompatible) pollen is discriminated from "non-self" (compatible) pollen by interaction of pollen and pistil S locus components and is subsequently inhibited. Our studies of the SI system in Papaver rhoeas have revealed that the pistil S locus protein, PrsS, is a small novel secreted protein that interacts with the pollen S locus protein, PrpS, which is a small novel transmembrane protein. This interaction of PrsS with incompatible pollen induces a SI response, involving a Ca 2+ -dependent signaling network, resulting in pollen inhibition and programmed cell death; this provides a neat way to destroy "self"-pollen. Several SI-induced events have been identifi ed, including Ca 2+ and K + infl ux, increases in cytosolic free Ca 2+ , activation of a MAP kinase, alterations to the cytoskeleton, and phosphorylation of a soluble inorganic pyrophosphatase. Here we present an overview of our knowledge of the novel cell-cell recognition S -determinants and the signals, targets, and mechanisms triggered by an incompatible interaction. We hope this review is of interest to those involved in the origins and evolution of cell-cell recognition systems involved in discrimination between "self" and "non-self," which include histocompatibility systems in primitive chordates and vertebrates as well as plant self-incompatibility.

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Protochordate allorecognition is controlled by a MHC-like gene system

Cited by 405 publications

References 14 publications

Reconstructing immune phylogeny: new perspectives

Reconstructing immune phylogeny: new perspectives

How One Thing Led to Another

Papaver rhoeas S-Determinants and the Signaling Networks They Trigger

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