Synthetic 5-amino-6-D-ribitylaminouracil paired with inflammatory stimuli facilitates MAIT cell expansion
5-amino-6-D-ribitylaminouracil (5-A-RU)
CpG
IL-23
MAIT cell boosting
MAIT cells
mouse model
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
28
11
2022
accepted:
12
07
2023
medline:
19
9
2023
pubmed:
18
9
2023
entrez:
18
9
2023
Statut:
epublish
Résumé
Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells, which mediate host immunity to microbial infection by recognizing metabolite antigens derived from microbial riboflavin synthesis presented by the MHC-I-related protein 1 (MR1). Namely, the potent MAIT cell antigens, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) and 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU), form via the condensation of the riboflavin precursor 5-amino-6-D-ribitylaminouracil (5-A-RU) with the reactive carbonyl species (RCS) methylglyoxal (MG) and glyoxal (G), respectively. Although MAIT cells are abundant in humans, they are rare in mice, and increasing their abundance using expansion protocols with antigen and adjuvant has been shown to facilitate their study in mouse models of infection and disease. Here, we outline three methods to increase the abundance of MAIT cells in C57BL/6 mice using a combination of inflammatory stimuli, 5-A-RU and MG. Our data demonstrate that the administration of synthetic 5-A-RU in combination with one of three different inflammatory stimuli is sufficient to increase the frequency and absolute numbers of MAIT cells in C57BL/6 mice. The resultant boosted MAIT cells are functional and can provide protection against a lethal infection of These results provide alternative methods for expanding MAIT cells with high doses of commercially available 5-A-RU (± MG) in the presence of various danger signals.
Identifiants
pubmed: 37720229
doi: 10.3389/fimmu.2023.1109759
pmc: PMC10500299
doi:
Substances chimiques
5-amino-6-D-ribitylaminouracil
0
Adjuvants, Immunologic
0
Pyruvaldehyde
722KLD7415
Riboflavin
TLM2976OFR
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1109759Informations de copyright
Copyright © 2023 Nelson, Wang, Dewar, Eddy, Li, Lim, Patton, Zhou, Pediongco, Meehan, Meehan, Mak, Fairlie, Stent, Kjer-Nielsen, McCluskey, Eckle, Corbett, Souter and Chen.
Déclaration de conflit d'intérêts
JM, DF, LK-N, JMc, SE, AC, and ZC are inventors of patents WO2014/005194 and WO2015/149130 describing MR1 tetramers and MR1 ligands. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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