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 investigate d in patients with recurrent oral ulcers (ROU). Peripheral blood monon uclear cells were stimulated with overlapping synthetic peptide (15(er s)), derived from the sequence of the 65-kD hsp of Mycobacterium tuber culosis. Specific lymphoproliferative responses were stimulated only w ith peptide 91-105 in ROU, compared with healthy or disease controls ( P < 0.01). This was confirmed by studying 760 short term cell lines ge nerated with the 65-kD hsp and then stimulated with the peptides, The frequency of short term cells lines responding to peptide 91-105 in RO U was significantly greater than in healthy (P < 0.0001) of disease co ntrols (P < 0.01). A comparative investigation with the homologous hum an 60-kD hsp peptide 116-130 also showed significantly greater lymphop roliferative responses in ROU than in healthy (P < 0.01) or disease co ntrols (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 98-105 during the stage of ulceration, compared with remission in 9/11 patients studied sequentially (P < 0.05). The results suggest that or al ulceration might be initiated by the microbial hsp peptide 91-105 s timulating the mucosal Langerhans cells, which may generate autoreacti ve T cell clones primed to the homologous peptide 116-130.