Fig 2: TRAV1-2 TCRs recognize CD1b, MHC-I and MR1.Overview of the TRAV1-2 TCRs in complex with CD1b (coloured white; a,b,g), MHC-I (coloured dark grey; c,d,h) and MR1 (coloured light grey; e,f,i) molecules. The top panels show the overview of each complex represented in cartoon format with the antigen in black spheres. The TRAV1-2 gene segment is coloured in light pink, the TRAJ gene segment in vibrant pink, and the β-chain in blue, orange and green for GEM42 TCR (a,b), ELS4 TCR (c,d) and MAIT TCR (e,f), respectively. A schematic of each TCR gene segment is represented as two rectangles for the α and β-chains, with TRAV1-2, TRAJ and the β-chains coloured as per the top panels. The middle panels show the footprint of each TCR on the surface of the CD1b-lipid (b), MHC-peptide (d) and MR1-metabolite (f). The black spheres on the middle panels represent the centre of mass of the Vα and Vβ domains, while the light grey spheres represent the antigen bound in each molecule. The atomic footprint is coloured according to the TCR segment making contact. The bottom panels show the TRAV1-2 gene segment (light pink) contact with (g) CD1b-lipid (white), (h) MHC-peptide (dark grey) and (i) MR1 (light grey).

Fig 3: Molecular tweezers grip the glucose headgroup of GMM.(a) Surface representation of the CDR3α (purple) and CDR3β (yellow) loops acting as ‘tweezers' grasping the GMM glucose head group (pale orange stick). (b) Schematic of the GMM analogues tested against the GEM T cells. Red shows the different hydroxyl orientation of Galactose monomycolate (MM) and Mannose MM. Each GMM analogue was used to stimulate IL-2 production upon presentation to GEM clone18 (black bar) and GEM clone 42 (pink bar), error bar representing triplicate wells. The experiments was performed twice with similar results. (c) Interaction network between the GMM (pale orange stick) and the GEM42 TCR (coloured as per Fig. 2a). The red dashed lines represent hydrogen bonds, while the blue dashed line represent hydrophobic interactions. (d) CDR3α loop sequences of the GEM TCR, element from the TRAV1-2 gene are highlighted in sand colour, N region in green and TRAJ9 gene in pink, while the CDR3β loop is coloured in yellow as per panel c.

Fig 4: Bias of the TCRα repertoire of MAIT cells from healthy control individuals (HCs, n = 5), immunological responders (IRs, n = 5) and immunological non-responders (INRs, n = 3). A The ratio of TRA V-J pairs in total MAIT cells. Large connecting lines denote a high proportion of V-J combinations. B Statistical analysis of TRAV1-2+/J33+ MAIT cell percentages among HCs, IRs and INRs. Data presented as mean ± SEM. Statistical analyses were performed using Fisher test. ∗P < 0.05.

Fig 5: Overview of the scRNA-seq results. A Transcript number per cell after data filtering in all samples. B The expression of marker genes that partitioned cells into 5 major clusters, namely, T cells, NK cells, monocytes, B cells and dendritic cells (DCs). C The expression of specific genes that identify the 8 cell subsets with the expression of TRAV1-2 and TRAJ33.