MR1T cells are T lymphocytes that recognize MR1-antigen complexes formed by small endogenous metabolites bound to MR1. They utilize various TCRs to detect different metabolites. A major group is activated by nucleoside carbonyl adducts, which accumulate preferentially in tumor cells, making MR1T cells promising for tumor immunotherapy.
When tested against a panel of 60 tumor cell lines representing both solid and liquid tumors, MR1T clones are divided into three groups based on their ability to recognize tumors, which depends on TCR and MR1 recognition. MR1T cells in the first group recognize almost all tested tumor cell lines. Those in the second group recognize about 50% of the tumor lines, while a third group of MR1T cells recognizes only a few of them.
Transcriptomic and metabolomic comparisons between leukemia cell lines with high or low stimulation capacity identified genes and metabolites that are overexpressed in stimulatory leukemic cells. Drug-mediated blockade of these pathways in tumor cells reduced MR1T cell stimulation, while drugs that enhance antigen and MR1 expression improved tumor cell recognition. These findings were confirmed in two mouse models of adoptive transfer of MR1T cells.
In summary, MR1T cells can monitor cell metabolic integrity. Because tumor cells often undergo metabolic shifts that produce more immunogenic metabolites, MR1T cells can target them.