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Identification of mouse cytomegalovirus immunoevasins that modulate NK cell recognition via the NKR-P1B:Clr-b axis (INM8P.403)

2015· article· en· W2747440548 on OpenAlexaff
James R. Carlyle, Jackeline Samaniego, Isabella Suzuki-Sampaio, Timothy Lau, Mir Munir A. Rahim, Branka Popović, Astrid Krmpotić, Stipan Jonjić, Andrew P. Makrigiannis, David Allan, Oscar A. Aguilar

Bibliographic record

VenueThe Journal of Immunology · 2015
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune Cell Function and Interaction
Canadian institutionsUniversity of OttawaSunnybrook HospitalUniversity of TorontoSunnybrook Health Science Centre
Fundersnot available
KeywordsComplementationBiologyMutantEctopic expressionCellPhenotypeReceptorLigand (biochemistry)Cell biologyGeneGenetics

Abstract

fetched live from OpenAlex

Abstract Natural killer (NK) cells are a subset of innate lymphoid cells (ILC) capable of recognizing pathological target cells through germline-encoded receptor-ligand interactions. Mouse cytomegalovirus (MCMV) is a beta-herpesvirus that has co-evolved with its murine host, and as such, a significant portion of its genome encodes immunoevasins that directly target NK cell receptor-ligand interactions. Here, we identify two putative immunoevasins that modulate host-pathogen interactions via the inhibitory NKR-P1B:Clr-b recognition system. First, we identify an m145 family member that actively prevents MCMV infection-mediated Clr-b downregulation. Ectopic expression of this m145 family member in mouse fibroblasts increases Clr-b expression at the cell surface. In contrast, infection with an m145-family deletion mutant shows more substantial Clr-b loss at the cell surface compared to wild-type MCMV infection. Importantly, enhanced Clr-b loss upon infection with the deletion mutant could be reversed by complementation experiments involving overexpression of the m145 family immunoevasin. Secondly, we have identified an immunoevasin that directly interacts with the NKR-P1B inhibitory receptor, suggestive of decoy ligand function. This interaction is MCMV strain-dependent and host NKR-P1B allele-specific, suggesting that polymorphisms have evolved at both the pathogen and host levels that affect NK cell recognition of infected target cells.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.028
GPT teacher head0.239
Teacher spread0.211 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2015
Admission routes1
Has abstractyes

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