Characterization of the TCRbeta repertoire of peripheral MR1-restricted MAIT cells in psoriasis vulgaris patients
Psoriasis vulgaris (PV) is an inflammatory skin disease largely driven by aberrant alpha-beta T cells. Mucosal-associated invariant T (MAIT) cells, which constitute the largest circulating innate-like alpha-beta T cell community in human adults, are characterized by a semi-invariant TCRVa7.2 receptor and MR1-restricted affinity toward microbial metabolites. Limited MAIT TCRa diversity is complemented by a more variable TCRbeta repertoire, but its footprint in the MAIT repertoire of PV patients has never been tested. Here, we used bulk RNASeq, MiXCR, VDJTools, and Immunarch pipelines to decipher and compare TCRbeta clonotypes from flow-sorted, peripheral TCRVa7.2+MR1-5-OP-RU-tet+MAIT cells from 10 PV patients and 10 healthy, matched controls. The resulting TCRbeta collections were highly private and individually unique, with small public clonotype content and high CDR3beta amino acid length variability in both groups. The age-related increase in the "hyperexpanded" clonotype compartment was observed in PV, but not in healthy MAIT repertoires. The TCRbeta repertoires of PV patients were also marked by preferential TRBV6-4 and TRBV11-2 gene usage, skewed TRBV/TRBJ pairing, and the emergence of PV-specific, public CDR3beta peptide sequences closely matching the published CDR3beta record from psoriatic skin. Overall, our study provides preliminary insight into the peripheral MAIT TCRbeta repertoire in psoriasis and warrants further evaluation of its diagnostic and clinical significance.