Dolton, Garry, Thomas, Hannah, Tan, Li Rong, Rius Rafael, Cristina ![]() ![]() ![]() ![]() ![]() ![]() |
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Abstract
The T cell antigen presentation platform MR1 consists of 6 allomorphs in humans that differ by no more than 5 amino acids. The principal function of this highly conserved molecule involves presenting microbial metabolites to the abundant mucosal-associated invariant T (MAIT) cell subset. Recent developments suggest that the role of MR1 extends to presenting antigens from cancer cells, a function dependent on the K43 residue in the MR1 antigen binding cleft. Here, we successfully cultured cancer-activated, MR1-restricted T cells from multiple donors and confirmed that they recognized a wide range of cancer types expressing the most common MR1*01 and/or MR1*02 allomorphs (over 95% of the population), while remaining inert to healthy cells including healthy B cells and monocytes. Curiously, in all but one donor these T cells were found to incorporate a conserved TCR-α chain motif, CAXYGGSQGNLIF (where X represents 3-5 amino acids), because of pairing between 10 different TRAV genes and the TRAJ42 gene segment. This semi-invariance in the TCR-α chain is reminiscent of MAIT cells and suggests recognition of a conserved antigen bound to K43.
Item Type: | Article |
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Date Type: | Published Online |
Status: | Published |
Schools: | Medicine |
Publisher: | American Society for Clinical Investigation |
ISSN: | 0021-9738 |
Date of First Compliant Deposit: | 20 January 2025 |
Date of Acceptance: | 29 October 2024 |
Last Modified: | 20 Jan 2025 15:06 |
URI: | https://orca.cardiff.ac.uk/id/eprint/175401 |
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