Shark class II invariant chain reveals ancient conserved relationships with cathepsins and MHC class II

Criscitiello, Michael F.; Ohta, Yuko; Graham, Matthew D.; Eubanks, Jeannine O.; Chen, Patricia L.; Flajnik, Martin F.

doi:10.1016/j.dci.2011.09.008

Cited by 35 publications

(21 citation statements)

References 82 publications

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“…It will be of interest to study how the lack of these catalysts impacts the association of peptides with MHC class II molecules; much work has been done on the biochemistry of MHC class II molecules in amphibians, but very little has been done in bony or cartilaginous fish 119 . However, the invariant chain (which is essential for the stable assembly of MHC class II molecules) is found in all ectotherms, with the attendant MHC class II-associated invariant chain peptide (CLIP) and the expected tissue distribution 120 .…”

Section: Evolution Of the Mhcmentioning

confidence: 99%

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: Evolution Of the Mhcmentioning

confidence: 99%

A cold-blooded view of adaptive immunity

2018

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“…T-cell receptor | MHC | evolution | mutation | variable region T he genes for immunoglobulins (Igs), αβ T-cell receptors (TCRs), and antigen-presenting MHC proteins appeared at least 450 million years ago in the cartilaginous fish and are present in all modern vertebrates (1)(2)(3). The more primitive hagfish and lampreys lack these genes and have an adaptive immune system comprised of unrelated proteins (4).…”

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confidence: 99%

Class II major histocompatibility complex mutant mice to study the germ-line bias of T-cell antigen receptors

Silberman

Krovi

Tuttle

et al. 2016

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

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The interaction of αβ T-cell antigen receptors (TCRs) with peptides bound to MHC molecules lies at the center of adaptive immunity. Whether TCRs have evolved to react with MHC or, instead, processes in the thymus involving coreceptors and other molecules select MHC-specific TCRs de novo from a random repertoire is a longstanding immunological question. Here, using nuclease-targeted mutagenesis, we address this question in vivo by generating three independent lines of knockin mice with single-amino acid mutations of conserved class II MHC amino acids that often are involved in interactions with the germ-line-encoded portions of TCRs. Although the TCR repertoire generated in these mutants is similar in size and diversity to that in WT mice, the evolutionary bias of TCRs for MHC is suggested by a shift and preferential use of some TCR subfamilies over others in mice expressing the mutant class II MHCs. Furthermore, T cells educated on these mutant MHC molecules are alloreactive to each other and to WT cells, and vice versa, suggesting strong functional differences among these repertoires. Taken together, these results highlight both the flexibility of thymic selection and the evolutionary bias of TCRs for MHC.T he genes for immunoglobulins (Igs), αβ T-cell receptors (TCRs), and antigen-presenting MHC proteins appeared at least 450 million years ago in the cartilaginous fish and are present in all modern vertebrates (1-3). The more primitive hagfish and lampreys lack these genes and have an adaptive immune system comprised of unrelated proteins (4). The main ligands for αβ TCRs are short peptides derived from self and foreign proteins, captured in a specialized groove of MHC class I (MHCI) and class II (MHCII) molecules and presented to T cells (5, 6). Functional Igs and TCRs are created by very similar recombination mechanisms involving fusion of V, J, and sometimes D gene segments with additional variations at the junctions to create an enormous potential repertoire of Igs and TCRs, suggesting a common, unknown evolutionary origin for these loci.These observations have raised several unanswered questions. For example,why did a separate TCR-rearranging gene system develop for lymphocytes recognizing peptide-MHC ligands? How did the extraordinarily polymorphic MHC genes stay functionally connected to TCR genes throughout 450 million years of evolution? One long-standing hypothesis has been that certain features of TCRs and MHC molecules are evolutionarily conserved to promote their interaction (7-10). Like Igs, the antigen-recognition portions of TCRs are partially encoded in the complementary determining region (CDR) CDR1 and CDR2 loops of germ-line TCR Vα (TRAV) and Vβ (TRBV) genes and are partially generated by somatic recombination processes that form the CDR3 loops. This initial repertoire is culled dramatically during T-cell development in the thymus. First, only those T cells whose TCRs have at least some minimal affinity for the selfpeptide-MHC molecules expressed in the thymus are positively selected for fu...

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“…As adaptive as some of the discussed nonvertebrate systems seem, clonal selection and tolerance thus far seem to be largely lacking or not understood, which may become important in new definitions. While “our” adaptive immunity surely evolved in a shark-like ancestor ∼460 million years ago [21]–[23] and has evolved tiers of regulation and complexity that should rightly dominate immunological research, we should also explore immunity in all life forms without preconceived notions of what we'll find. Are there other protein domains as often used for defensive repertoires as the IgSF and leucine-rich repeat?…”

Section: Resultsmentioning

confidence: 99%