Re-evaluation of the Immunological Big Bang

Flajnik, Martin F.

doi:10.1016/j.cub.2014.09.070

Cited by 69 publications

(46 citation statements)

References 49 publications

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“…This phenomenon was first discovered in the cartilaginous fish version of IgNAR 86 and soon after in marsupials 211 and other species as a single V domain, or VH domain, associated with the TCR Cδ chain. Consistent with old theories of γδ TCR function 212 , these findings suggest that γδ T cells in many vertebrates have adaptive functions 12 .…”

Section: Fig 1 |supporting

confidence: 81%

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A cold-blooded view of adaptive immunity

2018

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The adaptive immune system arose 500 million years ago in ectothermic (cold-blooded) vertebrates. Classically, the adaptive immune system has been defined by the presence of lymphocytes expressing recombination-activating gene (RAG)-dependent antigen receptors and the MHC. These features are found in all jawed vertebrates, including cartilaginous and bony fish, amphibians and reptiles and are most likely also found in the oldest class of jawed vertebrates, the extinct placoderms. However, with the discovery of an adaptive immune system in jawless fish based on an entirely different set of antigen receptors — the variable lymphocyte receptors — the divergence of T and B cells, and perhaps innate-like lymphocytes, goes back to the origin of all vertebrates. This Review explores how recent developments in comparative immunology have furthered our understanding of the origins and function of the adaptive immune system.

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Section: Fig 1 |supporting

confidence: 81%

“…1,2), as well as a thymus equivalent, the MHC has proved elusive; like the variable lymphocyte receptors (VLRs), an MHC may have arisen in this group via convergent evolution 11,12 . Mucosal adaptive immunity is present and unique for each group, as studied in amphibians and bony fish (and mammals) 13–15 .…”

mentioning

confidence: 99%

A cold-blooded view of adaptive immunity

2018

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“…Although sharks contain TCR-expressing lymphocytes (7, 8), recent genome sequence and transcriptome analyses of cartilaginous fish (elephant and nurse shark) have failed to identify a molecule with classical CD4 features, thus making teleosts the oldest living species with bona fide CD4 co-receptors (9–12). In contrast to the situation of tetrapods, which possess a single CD4 gene, bony fish contain two CD4 genes, cd4-1 and cd4-2 , which share low amino acid identity (~20%) (13, 14).…”

Section: Introductionmentioning

confidence: 99%

Novel Teleost CD4-Bearing Cell Populations Provide Insights into the Evolutionary Origins and Primordial Roles of CD4+ Lymphocytes and CD4+ Macrophages

Takizawa

Magadán

Parra

et al. 2016

The Journal of Immunology

105

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Tetrapods contain a single CD4 co-receptor with four immunoglobulin domains that likely arose from a primordial two-domain ancestor. Notably, teleost fish contain two CD4 genes. Like tetrapod CD4, CD4-1 of rainbow trout includes four immunoglobulin domains while CD4-2 contains only two. Since CD4-2 is reminiscent of the prototypic two-domain CD4 co-receptor, we hypothesized that by characterizing the cell types bearing CD4-1 and CD4-2, we would shed light into the evolution and primordial roles of CD4-bearing cells. Using newly established monoclonal antibodies against CD4-1 and CD4-2, we identified two bona fide CD4+ T-cell populations, a predominant lymphocyte population co-expressing surface CD4-1 and CD4-2 (CD4 DP), and a minor subset expressing only CD4-2 (CD4-2 SP). While both subsets produced equivalent levels of Th1, Th17, and Treg cytokines upon bacterial infection, CD4-2 SP lymphocytes were less proliferative and displayed a more restricted TCRβ repertoire. These data suggest that CD4-2 SP cells represent a functionally distinct population and may embody a vestigial CD4+ T cell subset, the roles of which reflect those of primeval CD4+ T cells. Importantly, we also describe the first CD4+ monocyte/macrophage population in a non-mammalian species. Of all myeloid subsets, we found the CD4+ population to be the most phagocytic, while CD4+ lymphocytes lacked this capacity. This study fills in an important gap in the knowledge of teleost CD4-bearing leukocytes thus revealing critical insights into the evolutionary origins and primordial roles of CD4+ lymphocytes and CD4+ monocyte/macrophages.

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“…Adaptive immunity based on germline rearrangement of leucine-rich repeat gene segments, along with a T/B dichotomy, has recently been demonstrated in agnathans (93). However, as “there has been no sign of MHC I or II genes in animals older than the cartilaginous fish” (94), it seems unlikely that a canonical DC population (at least one partially defined by MHC II expression) exists in the jawless vertebrates.…”

Section: Linking Innate and Adaptive Immunity Through Dendritic Cementioning

confidence: 99%

Evolution of Myeloid Cells

2016

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In 1882, Elie Metchnikoff identified myeloid-like cells from starfish larvae responding to the invasion by a foreign body (rose thorn). This marked the origins of the study of innate immunity, and an appreciation that cellular immunity is already well established in these “primitive” organisms. This chapter focuses on these myeloid cells as well as the newest members of this family, the dendritic cells (DC), and explores their evolutionary origins. Our goal is to provide evolutionary context for the development of the multilayered immune system of mammals, where myeloid cells now serve as central effectors of innate immunity and regulators of adaptive immunity. Overall, we find that core contributions of myeloid cells to the regulation of inflammation are based on mechanisms that have been honed over hundreds of millions of years of evolution. Using phagocytosis as a platform, we show how fairly simple beginnings have offered a robust foundation onto which additional control features have been integrated, resulting in central regulatory nodes that now manage multi-factorial aspects of homeostasis and immunity.

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Re-evaluation of the Immunological Big Bang

Cited by 69 publications

References 49 publications

A cold-blooded view of adaptive immunity

A cold-blooded view of adaptive immunity

Novel Teleost CD4-Bearing Cell Populations Provide Insights into the Evolutionary Origins and Primordial Roles of CD4+ Lymphocytes and CD4+ Macrophages

Evolution of Myeloid Cells

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