MR1-restricted T cell
There are two T-cell subsets recognising MR1 molecule: MAIT and autoreactive MR1T cells. MAIT cells are characterised by these properties: they express semi-invariant TCRs encoded by a TRAV1.2 TRAJ33/12/20 gene rearrangement; they can be stained by MR1-5-OP-RU tetramers; they express CD161, CD26 and CD218a markers; they express PLZF transcription factor; and they recognise and are activated by riboflavin metabolites. MR1T cells are a heterogeneous population and do not exhibit all these features, most commonly they don't express classical TRAV1-2 TCRs. They are various in expression of transcription factors, tissue distribution, function as well as in TCR repertoire and antigen specificity.[1]
Function of MR1T cells
MR1T cells do not recognise microbial antigens, especially compounds of the riboflavin pathway, or folate derivatives, such as MAIT cells. Instead of that, they recognise endogenous antigens and thus can react to tumor-associated antigens (TAA). Cancer cells express MR1 on the surface in constant low levels and that is the reason why MR1T cells do not react to healthy cells,[2] even they are presented in the blood of healthy individuals with a frequency between 1 in 2,500 and 1 in 5,000 in circulating T cells.[3] Because of that, they are considered as a promising tool in cancer immunotherapy.[4] Nevertheless, target antigens of these cells are still unknown. Currently it is known that antigens are: various, because different cells react to different fractions; stable within cell lysates; and conserved in mammals.[2]
MR1T express polyclonal repertoire of either TCRαβ or, with significantly less frequency, TCRγδ[1] and they can act as either Th1, Th2 or Th17 cells by cytokine release. The recognition is mediated by TCR and MR1 with bounded ligand.[4] Several of these cells can also express NK activatory and inhibitory receptors as well as immune-checkpoint receptors. Some of them can secrete large amounts of PDGFα and VEGF.[1] They are either CD8+ or double-negative and some cells can express CD161. They have tissue-homing capacity, but, in contrast to MAIT cells, their expression of CCR4 and CCR6 is low.[3]
Some MR1T cells are activated by non-riboflavin-related molecules and can react against infected cells in Th1-like manner. Thus, these cells can participate in antimicrobial immunity.[1] Other MR1T cells recognised in vitro differentiated monocyte-derived dendritic cells (DCs) and they promoted their maturation. Other cells responded to epithelial cell lines by cytokine releasing. That promoted expression of mucin, MR1T cells thus probably can be involved in epithelial cell function.[4]
MR1
The MHC-I-related molecule MR1 is, in contrast to classical MHC molecules, monomorphic and, in mammalians, strongly conserved molecule. In humans, it is expressed by most of nucleated cells in which it is kept in the endoplasmic reticulum until binding of an antigen. On the cell surface, there is generally a low number of MR1, but it can be increased during infection of the cell.[2]
Ligands of MR1
MR1 binds different classes of ligands.
According to the structure:
- The pyrimidine-based molecules with aromatic heterocyclic rings containing nitrogen at positions 1 and 3, such as doxofylline and mercaptopurine.[1]
- The molecules with a pteridine ring containing a keto group at position 4 and amino group at positions 2, such as 6-formylpterine and acetyl-6-formylpterine.[1]
- Small aromatic molecules, mostly drugs and drug-like metabolites, such as Aspirin, 3-formyl-salycilic acid and Diclofenac.[1]
According to the nature:
- Microbial antigens, mostly compounds of the riboflavin pathway, such as 7- hydroxy-6-methyl-8-D-ribityllumazine (RL-6-Me-7-OH) and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU).[1]
- Drugs, drug metabolites and drug-like molecules, such as mercaptopurine, 5-formyl-salicylic acid and Aspirin.[1]
- Self-antigens, probably metabolites abnormally synthesized and accumulated in cells during different conditions.[1]
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 De Libero, Gennaro; Chancellor, Andrew; Mori, Lucia (February 2021). "Antigen specificities and functional properties of MR1-restricted T cells". Molecular Immunology. 130: 148–153. doi:10.1016/j.molimm.2020.12.016. PMID 33358568 Check
|pmid=value (help). Unknown parameter|s2cid=ignored (help) - ↑ 2.0 2.1 2.2 Crowther, Michael D; Sewell, Andrew K (April 2021). "The burgeoning role of MR1-restricted T-cells in infection, cancer and autoimmune disease". Current Opinion in Immunology. 69: 10–17. doi:10.1016/j.coi.2020.12.002. PMID 33434741 Check
|pmid=value (help). Unknown parameter|s2cid=ignored (help) - ↑ 3.0 3.1 Vacchini, Alessandro; Chancellor, Andrew; Spagnuolo, Julian; Mori, Lucia; De Libero, Gennaro (2020-04-28). "MR1-Restricted T Cells Are Unprecedented Cancer Fighters". Frontiers in Immunology. 11: 751. doi:10.3389/fimmu.2020.00751. ISSN 1664-3224. PMC 7198878 Check
|pmc=value (help). PMID 32411144 Check|pmid=value (help). - ↑ 4.0 4.1 4.2 Mori, Lucia; De Libero, Gennaro (February 2020). "'Bohemian Rhapsody' of MR1T cells". Nature Immunology. 21 (2): 108–110. doi:10.1038/s41590-019-0588-6. ISSN 1529-2908. PMID 31959981. Unknown parameter
|s2cid=ignored (help)
This article "MR1-restricted T cell" is from Wikipedia. The list of its authors can be seen in its historical and/or the page Edithistory:MR1-restricted T cell. Articles copied from Draft Namespace on Wikipedia could be seen on the Draft Namespace of Wikipedia and not main one.
