Isolation and characterization of a protochordate histocompatibility locus

Tomaso, Anthony W. De; Nyholm, Spencer V.; Palmeri, Karla J.; Ishizuka, Katherine J.; Ludington, William B.; Mitchel, Katrina; Weissman, Irving L.

doi:10.1038/nature04150

Cited by 192 publications

(194 citation statements)

References 29 publications

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“…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 . Notably, again, a chimeric structure is involved in an immune-type function.…”

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%

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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“…Selon la vision traditionnelle fondée sur la morphologie comparée, l'histoire évolutive des Deutérostomiens est interprétée comme une marche progressive vers la complexité allant des formes « simples » vers les formes plus « complexes », lesquelles « culminent » Ainsi, la récente découverte d'un locus d'histocompatibilité chez l'Ascidie coloniale, Botryllus schlosseri, nous plonge directement aux origines de notre système immunitaire [8] tout en nous permettant de mieux comprendre le fonctionnement des cellules souches [9]. Comptant parmi les organismes producteurs de molé-cules aux propriétés anti-tumorales [10], les Tuniciers constituent, en outre, un réservoir potentiel de biomolécules naturelles qui ne demande qu'à être exploré.…”

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