scholarly journals Leprosy patients with lepromatous disease recognize cross-reactive T cell epitopes in the Mycobacterium leprae 10-kD antigen

1998 ◽  
Vol 114 (2) ◽  
pp. 204-209 ◽  
Author(s):  
Hussain ◽  
Dockrell ◽  
Shahid ◽  
Zafar ◽  
Chiang
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vinay Kumar Pathak ◽  
Itu Singh ◽  
Shoor Vir Singh ◽  
Utpal Sengupta

AbstractSeveral Mycobacterial infections including leprosy and tuberculosis are known to evoke autoimmune responses by modulating homeostatic mechanism of the host. Presence of autoantibodies like, rheumatoid factor, anti-nuclear factor and antibodies to host, collagen, keratin, myelin basic protein (MBP) and myosin, have been earlier reported in leprosy patients. In the present study, we detected the role of mimicking epitopes between Mycobacterium leprae and host components in the induction of autoimmune response in leprosy. Based on our previous findings, we predicted and synthesized a total of 15 mimicking linear B cell epitopes (BCE) and 9 mimicking linear T cell epitopes (TCE) of keratin and MBP. Humoral and cell-mediated immune responses against these epitopes were investigated in Non-reaction (NR), Type 1 reaction (T1R) leprosy patients, and healthy controls. We observed significantly higher levels of antibodies against 8 BCE in T1R in comparison to NR leprosy patients. Further, we also found 5 TCE significantly associated with lymphocyte proliferation in the T1R group. Our results indicated that these epitopes play a key role in the induction of autoimmune response in leprosy and are also strongly associated with the inflammatory episodes of T1R. Conclusively, these molecules may be employed as a biomarker to predict the inflammatory episodes of T1R.


2004 ◽  
Vol 72 (6) ◽  
pp. 3161-3170 ◽  
Author(s):  
John S. Spencer ◽  
Hee Jin Kim ◽  
Angela M. Marques ◽  
Mercedes Gonzalez-Juarerro ◽  
Monica C. B. S. Lima ◽  
...  

ABSTRACT Culture filtrate protein 10 (CFP-10) from Mycobacterium tuberculosis is a well-characterized immunodominant 10-kDa protein antigen known to elicit a very potent early gamma interferon response in T cells from M. tuberculosis-infected mice and humans. The sequence of the Mycobacterium leprae homologue of CFP-10 shows only 40% identity (60% homology) at the protein level with M. tuberculosis CFP-10 and thus has the potential for development as a T- or B-cell reactive antigen for specific diagnosis of leprosy. Antisera raised in mice or rabbits against recombinant M. leprae and M. tuberculosis CFP-10 proteins reacted only with homologous peptides from arrays of overlapping synthetic peptides, indicating that there was no detectable cross-reactivity at the antibody level. Sera from leprosy and tuberculosis patients were also specific for the homologous protein or peptides and showed distinct patterns of recognition for either M. leprae or M. tuberculosis CFP-10 peptides. At the cellular level, only 2 of 45 mouse T-cell hybridomas raised against either M. leprae or M. tuberculosis CFP-10 displayed a cross-reactive response against the N-terminal heterologous CFP-10 peptide, the region that exhibits the highest level of identity in the two proteins; however, the majority of peptide epitopes recognized by mouse T-cell hybridomas specific for each protein did not cross-react with heterologous peptides. Coupled with the human serology data, these results raise the possibility that peptides that could be used to differentiate infections caused by these two related microorganisms could be developed. Immunohistochemical staining of sections of M. leprae-infected nude mouse footpads resulted in strongly positive staining in macrophages and dendritic cells, as well as weaker staining in extracellular areas, suggesting that M. leprae CFP-10, like its homologue in M. tuberculosis, is a secreted protein.


2011 ◽  
Vol 80 (2) ◽  
pp. 742-752 ◽  
Author(s):  
Mehervani Chaduvula ◽  
A. Murtaza ◽  
Namita Misra ◽  
N. P. Shankar Narayan ◽  
V. Ramesh ◽  
...  

ABSTRACTLsr2 protein ofMycobacterium lepraewas shown earlier to elicit B and T cell responses in leprosy patients (20, 28). Lymphoproliferation toM. lepraeand Lsr2 antigens was observed in >70% of tuberculoid (T) patients and in 16 and 34% of lepromatous (L) patients, respectively. We focused on theM. lepraenonresponders in the lepromatous group using 22 synthetic Lsr2 peptides (end-to-end peptides A to F and overlapping peptides p1 to p16) inin vitroT 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 toP< 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 inducein vitroT cell responses in the highly infective lepromatous leprosy patients.


1988 ◽  
Vol 18 (6) ◽  
pp. 849-854 ◽  
Author(s):  
Wim C. A.Van Schooten ◽  
Tom H. M. Ottenhoff ◽  
Paul R. Klatser ◽  
Jelle Thole ◽  
René R. P.De Vries ◽  
...  

2001 ◽  
Vol 8 (3) ◽  
pp. 604-611 ◽  
Author(s):  
Anne Macfarlane ◽  
Rafael Mondragon-Gonzalez ◽  
Francisco Vega-Lopez ◽  
Brigitte Wieles ◽  
Josefina de Pena ◽  
...  

ABSTRACT The ability of the 45-kDa serine-rich Mycobacterium leprae antigen to stimulate peripheral blood mononuclear cell (PBMC) proliferation and gamma interferon (IFN-γ) production was measured in leprosy patients, household contacts, and healthy controls from areas of endemicity in Mexico. Almost all the tuberculoid leprosy patients gave strong PBMC proliferation responses to the M. leprae 45-kDa antigen (92.8%; n = 14). Responses were lower in lepromatous leprosy patients (60.6%;n = 34), but some responses to the 45-kDa antigen were detected in patients unresponsive to M. lepraesonicate. The proportion of positive responses to the M. leprae 45-kDa antigen was much higher in leprosy contacts (88%; n = 17) than in controls from areas of endemicity (10%; n = 20). None of 15 patients with pulmonary tuberculosis gave a positive proliferation response to the 45-kDa antigen. The 45-kDa antigen induced IFN-γ secretion similar to that induced by the native Mycobacterium tuberculosis30/31-kDa antigen in tuberculoid leprosy patients and higher responses than those induced by the other recombinant antigens (M. leprae 10- and 65-kDa antigens, thioredoxin, and thioredoxin reductase); in patients with pulmonary tuberculosis it induced lower IFN-γ secretion than the other recombinant antigens. These results suggest that the M. leprae 45-kDa antigen is a potent T-cell antigen which is M. leprae specific in these Mexican donors. This antigen may therefore have diagnostic potential as a new skin test reagent or as an antigen in a simple whole-blood cytokine test.


2002 ◽  
Vol 70 (2) ◽  
pp. 1010-1013 ◽  
Author(s):  
John S. Spencer ◽  
Maria Angela M. Marques ◽  
Monica C. B. S. Lima ◽  
Ana Paula Junqueira-Kipnis ◽  
Bruce C. Gregory ◽  
...  

ABSTRACT The sequence of the Mycobacterium leprae homologue of ESAT-6 shows only 36% amino acid correspondence to that from Mycobacterium tuberculosis. Anti-M. leprae ESAT-6 polyclonal and monoclonal antibodies and T-cell hybridomas reacted only with the homologous protein and allowed identification of the B- and T-cell epitopes. The protein is expressed in M. leprae and appears in the cell wall fraction. Thus, M. leprae ESAT-6 shows promise as a specific diagnostic agent for leprosy.


Sign in / Sign up

Export Citation Format

Share Document