Lsr2
protein of Mycobacterium leprae was shown earlier to elicit B and T cell responses in
leprosy patients (20, 28). Lymphoproliferation to M. leprae and Lsr2
antigens was observed in >70% of tuberculoid (T) patients and in 16 and 34% of lepromatous (L) patients, respectively. We focused on the M. leprae nonresponders in the lepromatous group using 22 synthetic Lsr2
peptides (end-to-end
peptides A to F and overlapping
peptides p1 to p16) in in vitro T cell responses. A total of 125
leprosy and 13
tuberculosis patients and 19 healthy controls from the area of endemicity (here, healthy controls, or HC) were investigated. The highest responses were observed (67 to 100%) in HC for all
peptides except p1 to p3, and the lowest was observed in
tuberculosis patients. Significant differences in lymphoproliferation were observed in T, L, and HC groups (analysis of variance [ANOVA], P = 0.000 to 0.015) for all end-to-end
peptides except B and for p5 and p7 to p10. Hierarchical recognition between lepromatous and
tuberculoid leprosy was noted for p8 (P < 0.05) and between the HC and L groups for p7 to p10, p15, and p16 (P < 0.005 to P < 0.02). Significant lymphoproliferation was observed to
peptides A to F and p1 to p9, p11, p12, p15, p16 (P = 0.000 to 0.001) with 40% responding to
peptides C and p16 in L patients. Lepromatous patients also showed significantly higher levels of a
gamma interferon (IFN-γ) response to
peptide C than to other
peptides (P < 0.05). Major histocompatibility complex (MHC) class II bias for
peptide recognition was not observed. These studies indicate that Lsr2 has multiple
T cell epitopes that induce in vitro T cell responses in the highly infective
lepromatous leprosy patients.