Figure 7. Significant correlations between IgG reactivity to specific AM OS motifs and Ab-mediated Mtb phagocytosis with TST⁺IGRA⁺ but not TB sera.

(A) Heterogeneous serum IgG reactivity to AM OS in both TST⁺IGRA⁺ and TB groups. Color features represent the mean fluorescence intensity (MFI) to each of the OS motifs. TST⁺IGRA⁺ subjects recognized many AM OS motifs with the same intensity as TB subjects (10% of color features in the TST⁺IGRA⁺ group and 9% of color features in the TB group exceeded the upper scale limit). Sera lined from left to right had IgG reactivity to native AM from high to low (minimum OD > 0.4). Compound S#46 is an OS motif of the mycobacterial capsular PS α-glucan, which served as a control. (B) Significant correlations between IgG reactivity to AM OS and Mtb phagocytosis were seen for 5 OSs with TST⁺IGRA⁺ (n = 10) but none of the 30 OSs with TB sera (n = 13; see also Supplemental Table 1). Spearman’s rank correlation. Red circles, TST^– control serum. (C) The 5 AM OSs recognized by TST⁺IGRA⁺ sera and significantly associated with Mtb phagocytosis share a common motif of 4 Araf residues (green stars) attached in the same configuration, β-(1→2), α-(1→5), α-(1→5), and further functionalized with additional mannose (green circles), inositol phosphate, or xylose (orange stars) residues. IgG reactivity to AM OSs 3, 6, and 12 also correlated with BCG phagocytosis in our prior studies with BCG immune sera (16). OS 3 recognition is significantly associated with phagocytosis with both TST⁺IGRA⁺ and BCG sera, while significant association with the other 2 motifs (6 and 12) was only seen with BCG immune sera.