Critical residues of the Mycobacterium leprae LSR recombinant protein discriminate clinical activity in erythema nodosum leprosum reactions

Singh, Swarandeep; Jenner, Peter; Narayan, N P; Ramu, G; Colston, M. J.; Prasad, H. K.; Nath, Indira

doi:10.1128/iai.62.12.5702-5705.1994

Cited by 19 publications

(8 citation statements)

References 10 publications

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“…Analysis of overlapping peptides spanning the M. leprae LSR sequence showed that two peptides (GVTYEIDLTNKNAA and IDLTNKNA AKLRGD) were recognized by the sera of leprosy patients (56). Single-residue deletions of the peptides enabled the identification of three distinct sequences (GVTY, NAA, and RGD) found to be important for antibody recognition (55). Although nothing is yet known of the M. tuberculosis homolog's role in the immune response, two of the three sequences important for antibody recognition in leprosy patients, GVTY and RGD, are present in its sequence.…”

Section: Proteins Of M Tuberculosis Modulated By Iron Proteins Of Mmentioning

confidence: 99%

Identification of Fur, Aconitase, and Other Proteins Expressed by Mycobacterium tuberculosis under Conditions of Low and High Concentrations of Iron by Combined Two-Dimensional Gel Electrophoresis and Mass Spectrometry

et al. 1999

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Iron plays a critical role in the pathophysiology ofMycobacterium tuberculosis. To gain a better understanding of iron regulation by this organism, we have used two-dimensional (2-D) gel electrophoresis, mass spectrometry, and database searching to study protein expression in M. tuberculosis under conditions of high and low iron concentration. Proteins in cellular extracts fromM. tuberculosis Erdman strain grown under low-iron (1 μM) and high-iron (70 μM) conditions were separated by 2-D polyacrylamide gel electrophoresis, which allowed high-resolution separation of several hundred proteins, as visualized by Coomassie staining. The expression of at least 15 proteins was induced, and the expression of at least 12 proteins was decreased under low-iron conditions. In-gel trypsin digestion was performed on these differentially expressed proteins, and the digestion mixtures were analyzed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry to determine the molecular masses of the resulting tryptic peptides. Partial sequence data on some of the peptides were obtained by using after source decay and/or collision-induced dissociation. The fragmentation data were used to search computerized peptide mass and protein sequence databases for known proteins. Ten iron-regulated proteins were identified, including Fur and aconitase proteins, both of which are known to be regulated by iron in other bacterial systems. Our study shows that, where large protein sequence databases are available from genomic studies, the combined use of 2-D gel electrophoresis, mass spectrometry, and database searching to analyze proteins expressed under defined environmental conditions is a powerful tool for identifying expressed proteins and their physiologic relevance.

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Section: Proteins Of M Tuberculosis Modulated By Iron Proteins Of Mmentioning

confidence: 99%

Identification of Fur, Aconitase, and Other Proteins Expressed by Mycobacterium tuberculosis under Conditions of Low and High Concentrations of Iron by Combined Two-Dimensional Gel Electrophoresis and Mass Spectrometry

et al. 1999

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“…With respect to B cell responses, erythema nodosum leprosum (ENL, type 2 reaction) in leprosy patients has been shown to be associated with antibody recognition of speci¢c sequences within the M. leprae LSR protein [16]. In addition, antibody recognition of critical residues within the LSR sequence can also be used for discrimination between clinically silent and active ENL [17]. However, any putative link between T cell responses against the LSR antigen and immunopathological conditions in tuberculoid leprosy has not yet been established.…”

Section: Introductionmentioning

confidence: 99%

Human T cell recognition of the Mycobacterium leprae LSR antigen: epitopes and HLA restriction

Oftung

Lundin²,

Meloen

et al. 1999

FEMS Immunology and Medical Microbiology

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We have in this work mapped epitopes and HLA molecules used in human T cell recognition of the Mycobacterium leprae LSR protein antigen. HLA typed healthy subjects immunized with heat killed M. leprae were used as donors to establish antigen reactive CD4+ T cell lines which were screened for proliferative responses against overlapping synthetic peptides covering the C-terminal part of the antigen sequence. By using this approach we were able to identify two epitope regions represented by peptide 2 (aa 29-40) and peptide 6 (aa 49-60), of which the former was mapped in detail by defining the N- and C-terminal amino acid positions necessary for T cell recognition of the core epitope. MHC restriction analysis showed that peptide 2 was presented to T cells by allogeneic cells coexpressing HLA-DR4 and DRw53 or DR7 and DRw53. In contrast, peptide 6 was presented to T cells only in the context of HLA-DR5 molecules. In conclusion, the M. leprae LSR protein antigen can be recognized by human T cells in the context of multiple HLA-DR molecules, of which none are reported to be associated with the susceptibility to develop leprosy. The results obtained are in support of using the LSR antigen in subunit vaccine design.

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“…73 More importantly, they showed that during ENL and prior to ENL the T cells recognized the sequences RGD, GVTY and NAA and these differ from the sequences of LSR2 recognized by the T cells of LL patients without ENL. [74][75][76] Therefore, LSR 2 and its peptides can be used in an IGRA assay for ENL diagnosis. Unfortunately, these observations were not confirmed by other investigators yet.…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Advances in leprosy immunology and the field application: A gap to bridge

Souza

Iyer

Lammas

et al. 2016

Clinics in Dermatology

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Advances concerning the hosts' immune response to Mycobacterium leprae infection have focused on elucidating the immune pathomechanisms involved, with the hope that predictive diagnostic and prognostic parameters (biomarkers) for field use would emerge; however, improvements in our understanding of the immunologic responses to this complex disease have, to date, somewhat failed to provide the effective and robust methods for improving its predictive diagnosis in the field situation, particularly in those patients suffering from paucibacillary disease. In this contribution we have attempted to review some of the advances both in the immunology and immunopathology of leprosy, and also highlight the limited clusters of immune parameters that are now available. Most importantly, we point out the limitations that still prevail in the provision of effective biomarkers in the field situation for either: (1) the diagnosis of indeterminate disease, (2) predictive diagnosis of individuals developing reactional states, (3) monitoring efficacy of treatment, or (4) monitoring treatment of reactional states.

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Critical residues of the Mycobacterium leprae LSR recombinant protein discriminate clinical activity in erythema nodosum leprosum reactions

Cited by 19 publications

References 10 publications

Identification of Fur, Aconitase, and Other Proteins Expressed by Mycobacterium tuberculosis under Conditions of Low and High Concentrations of Iron by Combined Two-Dimensional Gel Electrophoresis and Mass Spectrometry

Identification of Fur, Aconitase, and Other Proteins Expressed by Mycobacterium tuberculosis under Conditions of Low and High Concentrations of Iron by Combined Two-Dimensional Gel Electrophoresis and Mass Spectrometry

Human T cell recognition of the Mycobacterium leprae LSR antigen: epitopes and HLA restriction

Advances in leprosy immunology and the field application: A gap to bridge

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