Chemical insights into the search for MAIT cells activators

Natacha Veerapen; Judith Hobrath; Amareeta K Besra; Gurdyal S Besra

doi:10.1016/j.molimm.2020.11.017

Chemical insights into the search for MAIT cells activators

Natacha Veerapen, Judith Hobrath, Amareeta K Besra, Gurdyal S Besra

Biosciences

Research output: Contribution to journal › Article › peer-review

260 Downloads (Pure)

Abstract

Mucosal-associated invariant T cells (MAIT cells) represent a potential therapeutic target as they can tune or enhance immune responses. They recognise and become activated by antigens, presented by the monomorphic MHC-I related molecule, MR1. To assess the significance of MAIT cells in human diseases, a better understanding of the MAIT cell-MR1-antigen interaction is imperative. Easy access to MR1 ligands and MAIT cells activators can help achieve this. In this review, we summarise current literature that has identified the natural ligands and drug-like molecules that activate MAIT cells and provide insight into their key molecular interactions with MR1 and MAIT T cell receptors (TCRs). We focus on the progress made in synthesizing and isolating 5-amino-6-d-ribitylaminouracil (5-A-RU), a key precursor in the synthesis of the known natural ligands, 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil(5-OP-RU) and 5-(2-oxoethylideneamino)-6-d-ribitylaminouracil (5-OE-RU), and also on the stabilisation and optimisation of the latter compounds.

Original language	English
Pages (from-to)	114-120
Number of pages	7
Journal	Molecular immunology
Volume	129
Early online date	6 Dec 2020
DOIs	https://doi.org/10.1016/j.molimm.2020.11.017
Publication status	Published - Jan 2021

Bibliographical note

Funding Information:
GSB acknowledges support in the form of a Personal Research Chair from Mr. James Bardrick, a R oyal Society Wolfson Research Merit Award , and the Medical Research Council, UK (MR/R001154/1 and MR/S000542/1).

Keywords

Hydrogen-Bonding
MAIT activation
MR1 upregulation
Polar interaction
Schiff base
TCR recognition

ASJC Scopus subject areas

Immunology
Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.molimm.2020.11.017Licence: Creative Commons: Attribution (CC BY)

Veerapen_et_al_2021_Chemical_insights_into_the_search_for_MAIT_Molecular_ImmunologyFinal published version, 2.62 MBLicence: Creative Commons: Attribution (CC BY)

1 Finished
1 Active

The Mycobacterium tuberculosis Cell Envelope: unravelling complex cell wall assembly, degradation and re-cycling pathways
Besra, D. (Principal Investigator), Bhatt, A. (Co-Investigator), Futterer, K. (Co-Investigator), Alderwick, L. (Co-Investigator) & Zhang, J. (Co-Investigator)
Medical Research Council
1/03/19 → 28/02/25
Project: Research Councils
MICA: Addressing the burgeoning problem of tuberculosis: Exploiting phenotypic hits to identify new protein targets for drug discovery
Besra, D. (Principal Investigator), Cox, L. (Co-Investigator) & Futterer, K. (Co-Investigator)
Medical Research Council
1/04/18 → 31/03/22
Project: Research Councils

Cite this

@article{bfa08c7731d94be09be6b2acf1726428,

title = "Chemical insights into the search for MAIT cells activators",

abstract = "Mucosal-associated invariant T cells (MAIT cells) represent a potential therapeutic target as they can tune or enhance immune responses. They recognise and become activated by antigens, presented by the monomorphic MHC-I related molecule, MR1. To assess the significance of MAIT cells in human diseases, a better understanding of the MAIT cell-MR1-antigen interaction is imperative. Easy access to MR1 ligands and MAIT cells activators can help achieve this. In this review, we summarise current literature that has identified the natural ligands and drug-like molecules that activate MAIT cells and provide insight into their key molecular interactions with MR1 and MAIT T cell receptors (TCRs). We focus on the progress made in synthesizing and isolating 5-amino-6-d-ribitylaminouracil (5-A-RU), a key precursor in the synthesis of the known natural ligands, 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil(5-OP-RU) and 5-(2-oxoethylideneamino)-6-d-ribitylaminouracil (5-OE-RU), and also on the stabilisation and optimisation of the latter compounds.",

keywords = "Hydrogen-Bonding, MAIT activation, MR1 upregulation, Polar interaction, Schiff base, TCR recognition",

author = "Natacha Veerapen and Judith Hobrath and Besra, {Amareeta K} and Besra, {Gurdyal S}",

note = "Funding Information: GSB acknowledges support in the form of a Personal Research Chair from Mr. James Bardrick, a R oyal Society Wolfson Research Merit Award , and the Medical Research Council, UK (MR/R001154/1 and MR/S000542/1).",

year = "2021",

month = jan,

doi = "10.1016/j.molimm.2020.11.017",

language = "English",

volume = "129",

pages = "114--120",

journal = "Molecular immunology",

issn = "0161-5890",

publisher = "Elsevier",

}

TY - JOUR

T1 - Chemical insights into the search for MAIT cells activators

AU - Veerapen, Natacha

AU - Hobrath, Judith

AU - Besra, Amareeta K

AU - Besra, Gurdyal S

N1 - Funding Information: GSB acknowledges support in the form of a Personal Research Chair from Mr. James Bardrick, a R oyal Society Wolfson Research Merit Award , and the Medical Research Council, UK (MR/R001154/1 and MR/S000542/1).

PY - 2021/1

Y1 - 2021/1

N2 - Mucosal-associated invariant T cells (MAIT cells) represent a potential therapeutic target as they can tune or enhance immune responses. They recognise and become activated by antigens, presented by the monomorphic MHC-I related molecule, MR1. To assess the significance of MAIT cells in human diseases, a better understanding of the MAIT cell-MR1-antigen interaction is imperative. Easy access to MR1 ligands and MAIT cells activators can help achieve this. In this review, we summarise current literature that has identified the natural ligands and drug-like molecules that activate MAIT cells and provide insight into their key molecular interactions with MR1 and MAIT T cell receptors (TCRs). We focus on the progress made in synthesizing and isolating 5-amino-6-d-ribitylaminouracil (5-A-RU), a key precursor in the synthesis of the known natural ligands, 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil(5-OP-RU) and 5-(2-oxoethylideneamino)-6-d-ribitylaminouracil (5-OE-RU), and also on the stabilisation and optimisation of the latter compounds.

AB - Mucosal-associated invariant T cells (MAIT cells) represent a potential therapeutic target as they can tune or enhance immune responses. They recognise and become activated by antigens, presented by the monomorphic MHC-I related molecule, MR1. To assess the significance of MAIT cells in human diseases, a better understanding of the MAIT cell-MR1-antigen interaction is imperative. Easy access to MR1 ligands and MAIT cells activators can help achieve this. In this review, we summarise current literature that has identified the natural ligands and drug-like molecules that activate MAIT cells and provide insight into their key molecular interactions with MR1 and MAIT T cell receptors (TCRs). We focus on the progress made in synthesizing and isolating 5-amino-6-d-ribitylaminouracil (5-A-RU), a key precursor in the synthesis of the known natural ligands, 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil(5-OP-RU) and 5-(2-oxoethylideneamino)-6-d-ribitylaminouracil (5-OE-RU), and also on the stabilisation and optimisation of the latter compounds.

KW - Hydrogen-Bonding

KW - MAIT activation

KW - MR1 upregulation

KW - Polar interaction

KW - Schiff base

KW - TCR recognition

UR - http://www.scopus.com/inward/record.url?scp=85097468528&partnerID=8YFLogxK

U2 - 10.1016/j.molimm.2020.11.017

DO - 10.1016/j.molimm.2020.11.017

M3 - Article

C2 - 33293098

SN - 0161-5890

VL - 129

SP - 114

EP - 120

JO - Molecular immunology

JF - Molecular immunology

ER -

Chemical insights into the search for MAIT cells activators

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Fingerprint

Projects

The Mycobacterium tuberculosis Cell Envelope: unravelling complex cell wall assembly, degradation and re-cycling pathways

MICA: Addressing the burgeoning problem of tuberculosis: Exploiting phenotypic hits to identify new protein targets for drug discovery

Cite this