MR1-restricted T cell clonotypes are associated with resistance to <i>Mycobacterium tuberculosis</i>infection

Abstract T-cells are a critical facet of the adaptive immune system and have been shown in both human animal studies to be essential for control Mycobacterium tuberculosis (Mtb) infection. recognize foreign antigens presented by infected cells via unique T-cell receptor (TCR). Understanding specific TCRs that mediate recognition clearance Mtb-infected is inform vaccine design. We recently described cohort Ugandan household contacts cases appear ‘resist’ Mtb infection (RSTRs) showed these individuals harbor IFN-γ independent responses peptide antigens. The role unconventional non-peptide antigens, such as gd T-cells, CD1-restricted MR1-restricted (MR1T), “resistance” unknown. In this study, we aimed characterize frequencies, functional programs, repertoire RSTRs comparison with latently (LTBI) controls. used multi-parameter flow cytometry, single cell RNA TCR sequencing immunosequencing address gaps. observed 1.65-fold increase frequency circulating MR1T among LTBI (p=0.03). Single-cell RNA-sequencing 18,251 sorted revealed 5,150 clonotypes expressing common transcriptional program, majority which were private. Immunosequencing TCR-α/d several TCRα expanded (p &amp;lt;0.01), including at least two clonotypes. Overall, our data reveal unexpected donor-specific diversity well associations between MR1 ‘resistance’ This work was supported grants from NIH (R01-AI124348 Boom, Stein, Hawn; R01-AI125189 R01-AI146072 Seshadri) Bill &amp; Melinda Gates Foundation (OPP1151836 OPP1109001 Hawn GH-VAP-IS-ID5 Seshadri).