Dataset Information

The Mechanism of ?2m Molecule-Induced Changes in the Peptide Presentation Profile in a Bony Fish.

ABSTRACT: Contemporary antigen presentation knowledge is based on the existence of a single ?2m locus, and a classical MHC class I forms a complex with a peptide (i.e., pMHC-I) to trigger CTL immunity. However, two ?2m loci have been found in diploid bony fish; the function of the two ?2m molecules is unclear. Here, we determined the variant peptide profiles originating from different products of the ?2m loci binding to the same MHC-I molecule and further solved the crystal structures of the two pMHC-I molecules (i.e., pCtid-UAA-?2m-2 and pCtid-UAA-?2m-1-II). Of note, in pCtid-UAA-?2m-2, a unique hydrogen bond network formed in the bottom of the peptide-binding groove (PBG) led to ?2-helix drift, ultimately leading to structural changes in the PBG. The mechanism of the change in peptide presentation profiles by ?2m molecules is illustrated. The results are also of great significance for antivirus and antitumor functions in cold-blooded vertebrates and even humans.

SUBMITTER: Li Z

PROVIDER: S-EPMC7240133 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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The Mechanism of β2m Molecule-Induced Changes in the Peptide Presentation Profile in a Bony Fish.

Li Zibin Z Zhang Nianzhi N Ma Lizhen L Zhang Lijie L Meng Geng G Xia Chun C

iScience 20200430 5

Contemporary antigen presentation knowledge is based on the existence of a single β2m locus, and a classical MHC class I forms a complex with a peptide (i.e., pMHC-I) to trigger CTL immunity. However, two β2m loci have been found in diploid bony fish; the function of the two β2m molecules is unclear. Here, we determined the variant peptide profiles originating from different products of the β2m loci binding to the same MHC-I molecule and further solved the crystal structures of the two pMHC-I mo ...[more]

PMID: 32438322

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Project description:BackgroundViruses can impose energetic demands on organisms they infect, in part by hosts mounting resistance. Recognizing that oxygen uptake reliably indicates steady-state energy consumption in all vertebrates, we comprehensively evaluated oxygen uptake and select transcriptomic messaging in sockeye salmon challenged with either a virulent rhabdovirus (IHNV) or a low-virulent reovirus (PRV). We tested three hypotheses relating to the energetic costs of viral resistance and tolerance in this vertebrate system: (1) mounting resistance incurs a metabolic cost or limitation, (2) induction of the innate antiviral interferon system compromises homeostasis, and (3) antiviral defenses are weakened by acute stress.ResultsIHNV infections either produced mortality within 1-4 weeks or the survivors cleared infections within 1-9 weeks. Transcription of three interferon-stimulated genes (ISGs) was strongly correlated with IHNV load but not respiratory performance. Instead, early IHNV resistance was associated with a mean 19% (95% CI = 7-31%; p = 0.003) reduction in standard metabolic rate. The stress of exhaustive exercise did not increase IHNV transcript loads, but elevated host inflammatory transcriptional signaling up to sevenfold. For PRV, sockeye tolerated high-load systemic PRV blood infections. ISG transcription was transiently induced at peak PRV loads without associated morbidity, microscopic lesions, or major changes in aerobic or anaerobic respiratory performance, but some individuals with high-load blood infections experienced a transient, minor reduction in hemoglobin concentration and increased duration of excess post-exercise oxygen consumption.ConclusionsContrary to our first hypothesis, effective resistance against life-threatening rhabdovirus infections or tolerance to high-load reovirus infections incurred minimal metabolic costs to salmon. Even robust systemic activation of the interferon system did not levy an allostatic load sufficient to compromise host homeostasis or respiratory performance, rejecting our second hypothesis that this ancient innate vertebrate antiviral defense is itself energetically expensive. Lastly, an acute stress experienced during testing did not weaken host antiviral defenses sufficiently to promote viral replication; however, a possibility for disease intensification contingent upon underlying inflammation was indicated. These data cumulatively demonstrate that fundamental innate vertebrate defense strategies against potentially life-threatening viral exposure impose limited putative costs on concurrent aerobic or energetic demands of the organism.

Dataset Information

The Mechanism of ?2m Molecule-Induced Changes in the Peptide Presentation Profile in a Bony Fish.

Publications

The Mechanism of β2m Molecule-Induced Changes in the Peptide Presentation Profile in a Bony Fish.

Similar Datasets

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