Recognition of a Unique Peptide Epitope of the Mycobacterial and Human Heat Shock Protein 65-60 Antigen by T Cells of Patients with Recurrent Oral Ulcers

T cell epitopes of the 65-kD heat shock protein (hsp) were investigated in patients with recurrent oral ulcers (ROU). Peripheral blood mononuclear cells were stimulated with overlapping synthetic peptide (15ers), derived from the sequence of the 65-kD hsp of Mycobacterium tuberculosis. Specific lymphoproliferative responses were stimulated only with peptide 91-105 in ROU, compared with healthy or disease controls (P < 0.01). This was confirmed by studying 760 short term cell lines generated with the 65-kD hsp and then stimulated with the peptides. The frequency of short term cells lines responding to peptide 91-105 in ROU was significantly greater than in healthy (P < 0.0001) or disease controls (P < 0.01). A comparative investigation with the homologous human 60-kD hsp peptide 116-130 also showed significantly greater lymphoproliferative responses in ROU than in healthy (P < 0.01) or disease controls (P < 0.001). The potential involvement of the T cell epitope 91-105 in the pathogenesis of ROU is supported by finding a significant increase in the lymphoproliferative responses stimulated with peptide 91-105 during the stage of ulceration, compared with remission in 9/11 patients studied sequentially (P < 0.05). The results suggest that oral ulceration might be initiated by the microbial hsp peptide 91-105 stimulating the mucosal Langerhans cells, which may generate autoreactive T cell clones primed to the homologous peptide 116-130.