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

Abstract

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...

Detection, Enumeration and Characterization of T Helper Cells Secreting Type 1 and Type 2 Cytokines in Patients with Recurrent Aphthous Stomatitis

“…This is achieved with its capability to recognize the mali- cious antigens and to prevent their catastrophic action as well as the autodestructive immune response. Given that there is no difference between the foreign body and the autoantigen, some authors suggested that the cells of the immune system react to the antigens only by the presence of cytokines (Hasan et al 2002).…”

Recurrent aphthous stomatitis

“…Hypersensitivity to certain food substances, oral microbes such as Streptococcus sanguis, and microbial heat shock protein have been suggested as possible causative factors, but there is still no conclusive evidence to support allergy as a major cause of RAS 48,49 . Although some studies reported that RAS patients tend to have hypersensitivity to environmental allergens, other reports did not find significant correlation between hypersensitivity and RAS.…”

“…Early work suggested a relationship between several immune-mediated reactions and development of RAS. These include cytotoxicity of T lymphocytes to oral epithelium, antibody-dependent cell-mediated cytotoxicity, and defects in lymphocyte subpopulations 49,54,55 . One theory is that multiple immune reactions cause damage induced by deposition of immune complexes within the oral epithelium.…”

Characterization of recurrent aphthous stomatitis in a young population

“…Hypersensitivity to some food components and oral microbial agents are considered potential etiological factors. 1,16,17 The association between RAS and some nutritional and blood deficits has been studied, and patients with RAS have been proved to present iron, B12 vitamin, folic acid and hemoglobin deficits more frequently. 18 The fact that 5-10% of patients with RAS present low blood levels of folate, zinc, iron, and B1, B2, B6 and B12 vitamins may suggest these nutritional deficits as potential causes.…”