Association of the Mycobacterial 30‐kDa Region Proteins with the Cutaneous Infiltrates of Leprosy Lesions

Rambukkana, Anura; Das, Pranab K.; Krieg, S. R.; Faber, William R.

doi:10.1111/j.1365-3083.1992.tb02938.x

Cited by 19 publications

(4 citation statements)

References 36 publications

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“…The 85B proteins are important immunogenic components of the cell walls of M. tuberculosis (4) and, consequently, may persist at the sites of infection. Rambukkana and colleagues have demonstrated the presence of M leprae 85B protein both in the cell walls of the bacillus and as an extracellular protein in the cutaneous lesions of leprosy patients (25,26). The current study confirms that the recombinant 85B protein of M bovis, MPB59, which is almost identical to its M tuberculosis counterpart, is an important T-cell antigen, being recognized by more than 95% of BCG vaccinees and half of TB patients.…”

Section: Discussionsupporting

confidence: 80%

T-cell determinants and antibody binding sites on the major mycobacterial secretory protein MPB59 of Mycobacterium bovis

et al. 1994

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Among the first proteins encountered by the host immune system upon infection or vaccination with mycobacteria are those secreted by the bacillus during growth. The antigen 85 complex of Mycobacterium bovis bacillus Calmette-Guerin (BCG) is composed of three closely related members. The mature 85B protein of M. bovis (MPB59) has a high degree of amino acid identity with the M. bovis 85A protein (76%) and the Mycobacterium tuberculosis 85B (99%o) and 85A (76%) proteins. We have examined the regions of MPB59 which stimulate human T-and B-cell responses by use of a set of 28 synthetic peptides, 20 amino acids (aa) in length and overlapping by 10 aa. Initial proliferative assays with recombinant MPB59 demonstrated that peripheral blood mononuclear cells from 95% of BCG vaccinees and 52% of tuberculosis patients responded to the whole mature protein. Peripheral blood mononuclear cells from MPB59 responders, but not nonresponders, were stimulated by peptides in a dose-dependent fashion. Five peptides were reactive in more than half of the MPB59 responders. The T-cell-reactive regions were essentially identical in the M. bovis and M. tuberculosis 85B proteins. Subjects with a variety of HLA-DR phenotypes responded to a number of these peptides. The dominant T-cell-reactive regions were distinct from the peptides recognized by sera from tuberculosis patients (aa 71 to 100) and the murine monoclonal antibody HYT27 (aa 61 to 90). The region reactive with antibodies overlapped part of the MPB59 sequence recently shown to participate in the binding of MPB59 to fibronectin. . MATERIALS AND METHODSAntigens. (i) Recombinant MPB59 protein. A 974-bp fragment encoding the gene sequence for the mature MPB59 protein (20) was generated by PCR from M. bovis (strain AN5) chromosomal DNA, cloned into the BamHI and SmaI sites in the pGEX-2T vector (33), and expressed in Escherichia coli JM109. The recombinant protein, expressed as a fusion product with glutathione S-transferase (GST), was purified from cell sonicate by affinity chromatography with glutathione agarose, and the MPB59 protein was cleaved from the GST 5319 on August 6, 2020 by guest http://iai.asm.org/ Downloaded from

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Section: Discussionsupporting

confidence: 80%

T-cell determinants and antibody binding sites on the major mycobacterial secretory protein MPB59 of Mycobacterium bovis

et al. 1994

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“…Shetty et al 11 have also found that antigen staining within nerves occurs predominantly in macrophages and epithelioid cells. The noncellular diffuse infiltrate associated staining pattern we observed has also been reported by Rambukkana et al, 12 who noted this type of staining in a skin biopsy from a multibacillary patient with a type I reaction. The strength of staining seen in these biopsies suggests that there is a relative abundance of antigen in type I reactions; staining is much stronger than in new paucibacillary patients and all types of treated patient.…”

Section: Discussionsupporting

confidence: 66%

The detection of Mycobacterium leprae protein and carbohydrate antigens in skin and nerve from leprosy patients with type 1 (reversal) reactions.

Lockwood¹,

Colston²,

Khanolkar-Young³

2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. Type 1 (reversal) reactions are the most common immunological complications of leprosy. These episodes of delayed hypersensitivity produce severe local immunopathology and ultimately nerve damage. To date, the Mycobacterium leprae antigens associated with type 1 reactions have not been identified. Using monoclonal antibodies to defined protein and carbohydrate M. leprae epitopes (65, 35 and 28 kd and lipoarabinomannan [LAM]) in a two-step immunoperoxidase staining technique, M. leprae antigens were demonstrated in skin and nerve biopsies from patients in reversal reaction. Antigen presence and staining patterns were similar in skin and nerve lesions, implying that the pathological processes are similar in the two sites. Antigens were present both in macrophages and Schwann cells but also as a diffuse extracellular infiltrate associated with the inflammatory infiltrate. The 28-kd antigen was present most strongly and may be a potential candidate antigen for initiating type 1 reactions. LAM also stained strongly and persisted after treatment. The possible roles of LAM and 65 kd in the cellular events of type 1 reactions are discussed.

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“…In fact, monocyte agglutination activity of human T-cell FN has been shown to be significantly inhibited by α-Ag in itro [38]. It was reported that the production of α-Ag is increased at tissue sites where mycobacteria grow [39]. α-Ag might therefore be expected to modify the local effective response of host lymphocytes against infected mycobacteria.…”

Section: Discussionmentioning

confidence: 99%

The domains of human fibronectin mediating the binding of α antigen, the most immunopotent antigen of mycobacteria that induces protective immunity against mycobacterial infection

et al. 2000

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We have recently shown that alpha antigen (alpha-Ag), the immunodominant antigen of mycobacteria, has a novel fibronectin (FN)-binding motif that is unique among mycobacteria [Naito, Ohara, Matsumoto and Yamada (1998) J. Biol. Chem. 273, 2905-2909]. In this study, we examined the domains of human FN that interacted with alpha-Ag. Fragments of FN generated by either proteolysis or recombinant DNA techniques were compared for their ability to bind to alpha-Ag. Fragments containing either the C-terminal heparin-binding domain or the central cell-binding domain consistently bound to alpha-Ag. The fragment of the C-terminal heparin-binding domain, upon mutation that resulted in the loss of its heparin-binding activity, could not bind with alpha-Ag. These findings suggested that the mutated site, i.e. the main heparin-binding site of FN, was also the principal site for binding to alpha-Ag. The alpha-Ag-binding domains of FN could bind whole mycobacterial bacilli, suggesting that these two domains are important contributors to mycobacterial infection.

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Association of the Mycobacterial 30‐kDa Region Proteins with the Cutaneous Infiltrates of Leprosy Lesions

Cited by 19 publications

References 36 publications

T-cell determinants and antibody binding sites on the major mycobacterial secretory protein MPB59 of Mycobacterium bovis

T-cell determinants and antibody binding sites on the major mycobacterial secretory protein MPB59 of Mycobacterium bovis

The detection of Mycobacterium leprae protein and carbohydrate antigens in skin and nerve from leprosy patients with type 1 (reversal) reactions.

The domains of human fibronectin mediating the binding of α antigen, the most immunopotent antigen of mycobacteria that induces protective immunity against mycobacterial infection

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