Immunological study of the defined constituents of mycobacteria

Recurrent aphthous stomatitis (RAS) is the most common disease of the oral mucosa, affecting at least 10% of the general population [1]. The onset of RAS usually presents during adolescence, and the course of the disease is characterized by recurrences followed by remissions. The disease may persist for many years and varies from minor ulcers, which may cause transient discomfort, to major ulcers which are associated with pain, inability to eat and loss of weight [2].The aetiology of RAS has not been determined, but Streptococcus sanguis or its L-form [3,4] has been implicated, as has autoimmunity to the oral mucosal homogenate [5][6][7]. A common or cross-reactive antigen between streptococci and oral epithelium has been suggested [6][7][8][9] and demonstrated between the streptococcal 60-65 kD heat shock protein (HSP) and oral mucosal tissue [10]. Significant increase in serum antibodies to HSP has been detected in patients with RAS [10].Heat shock proteins (HSP) are a group of highly conserved proteins found in eukaryotic and prokaryotic cells, including Gram-positive and Gram-negative micro-organisms [11,12]. Viruses can enhance the production of host HSP. The high degree of homology between microbial and human HSP 60 [13] has led to the concept that molecular mimicry between the microbial and self HSP may be involved in the pathogenesis of autoimmune diseases [14]. A comprehensive investigation of T-cell epitopes within the 65 kD mycobacterial-and 60 kD human HSP-derived peptides has identified four T-cell epitopes specific for Behcet's disease, in which oral ulceration is the most consistent manifestation [15]. All but one of the four peptides (amino acids 219-233) showed significantly greater stimulation of lymphocytes from patients with Behcet's disease than those from RAS. However, the investigation raised the possibility that another peptide (amino acids 91-105) might specifically stimulate lymphocytes from RAS and not Behcet's disease. Indeed, specific lymphoproliferative responses are stimulated with peptide 91-105 in RAS [16]. A comparative investigation with the homologous human 60 kD HSP peptide 116-130 also revealed significantly greater lymphoproliferative responses in RAS than in controls.The objectives of this investigation in patients with RAS were to define the critical residues within the T-cell epitope 91-105, and to investigate the role of HLA class I and II restriction elements in the lymphoproliferative response. The possibility that g d T cells may be involved was also explored. 318 Defining a T-cell epitope within HSP 65 in recurrent aphthous stomatitis SUMMARYThe 65 kD heat shock protein (HSP) has been implicated in the aetiology of recurrent aphthous stomatitis (RAS). We have previously demonstrated that peptide 91-105 derived from the sequence of mycobacterial 65 kD HSP stimulates specifically lymphocytes from patients with RAS. In this investigation, we show that both CD4 + and CD8 + T cells were significantly stimulated with mycobacterial peptide 91-105. In contrast, the human h...

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Defining a T-cell epitope within HSP 65 in recurrent aphthous stomatitis

Hasan¹,

Shinnick

Mizushima

et al. 2002

“…An estimate of the relative potency of the purified antigens as T cell immunogens can be obtained by carrying out a correlation analysis ofthe proliferative responses to them versus the whole sonicates which contain a broad spectrum of antigens (Ivanyi et at., 1988). In order to minimize variations related to disease category, the analysis was performed on the data from the contacts and the results from paiients were excluded.…”

Section: Correlation Between Protiferative Responses To Purified and mentioning

confidence: 99%

T cell reactivity to the purified mycobacterial antigens p65 and p70 in leprosy patients and their household contacts

Adams

Garsia

Hellqvist

et al. 1990

SUMMARYT cell reactivity to the 70 and 65 kD (p70 and p65) protein antigens derived from Mycobacterium bovis BCG strain was studied by measuring the proliferative responses of peripheral blood mononuclear cells from members ofan isolated Aboriginal eommunity resident in the Torres Straits islands. In tbe nine index leprosy cases the pattern of responsiveness to the purified antigens paralleled that to whole sonicates from M. leprae and BCG. In the 40 contacts of tbe index cases, a high correlation was observed between the responses to p70 and p65 as well as to the crude sonicates. Significant T cell responses to the purified antigens, as well as the erude sonicates, were obtained with cells from the majority of contacts. Limiting dilution analysis of precursor frequencies in tbe contacts confirmed the immunogenicity of the purified antigens and excluded both a mitogenie component and tbe presence of suppressor cells in those moderate or low responders whose blood contained sufficient precursors to be tested. p70 appeared to be more potent in stimulating a proliferative response than p65 at equivalent protein concentrations. No correlation between responder status to cither antigen and disease type was detected in families. These findings provide confirmation of the importance of p70 and p65 as major T cell immunogens in man and indicate that they are botb potential candidates for inclusion in a bivalent vaccine for leprosy and tuberculosis.

“…24 and 18 kD, have been selected for serologieal analysis with the human sera. Of these antigens, the 38-kD seems to be related to a major immunogen of tuberelc bacilli [19][20][21], the 24-kD antigens represented by at least two distinet constituents have no proven relationship to any ofthe mycobacterial proteins of known structure, whereas the 18-kD proteaseresistant antigen probably eorresponds to the MAP baeterioferritin [16].…”

Section: Introductionmentioning

confidence: 99%

Antibodies to Mycobacterium paratuberculosis-specific protein antigens in Crohn's disease

Elsaghier

Prantera

Moreno

et al. 1992

SUMMARYThe possible role of infection with Mycobacterimn parattiherculo,sis (MAP) for the etiopathogenesis of Crohn's disease (CD) has been a matter of long-term controversy. In addition to similarities with the pathology of ruminant paratubereulosis, DNA tingerprinting eonfirmed the organism isolated from gut tissue, but thespecificity of the immune repertoire has not as yet been evaluated. We report here on a serologieal study of 29 patients with CD, 20 patients with ulcerative colitis and 18 healthy control subjects, using three antigens attributed with species-specificity and selective immunogenicity following MAP infection. Antibodies binding to the 38-kD band of MAP extract were demonstrable by the Western blot technique in 57% of CD patients. Antibody levels to the 24-kD (p24BCD) eathodic bands, determined by competition ELiSA using a monospecitic niuHne antiserum, and to the 18-kD protease-resistant purified baeterioferritin. delected by standard ELISA. were significantly elevated in 53'yu of CD patients. However, these three antibody specificities tested in individual CD patients did not show any correlation with eaeh other. Thus. 18''^ ofpatients were positive for all three specificities, whilst 84% had antibodies to at least one of the specifie antigens. Although the exact proportion of affected patients is yet to be defined, the serologieal results obtained support the view that MAP infeetion may play an etiological role in Crohn's disease.