T-CELL EPITOPE EXPRESSION OF MYCOBACTERIAL AND HOMOLOGOUS HUMAN 65-KILODALTON HEAT-SHOCK PROTEIN-PEPTIDES IN SHORT-TERM CELL-LINES FROM PATIENTS WITH BEHCETS-DISEASE

T cell epitopes of the 65-kDa heat shock protein (HSP) were mapped in patients with Behcet's disease (BD), by stimulating T cells with the o verlapping synthetic peptides derived from the sequences of the Mycoba cterium tuberculosis 65-kDa HSP. Significant lymphoproliferative respo nses were stimulated with four HSP peptides in BD, as compared with th e related disease (recurrent oral ulcers), unrelated disease, and heal thy controls (p < 0.05 to 0.005). In order to assess the relative freq uency of sensitized lymphocytes by these peptides, 7353 short term cel l lines were generated from the lymphocytes of patients and controls. Peptides 111-125, 154-172, and 311-325 (p < 0.001) and peptide 219-233 (p < 0.02) yielded significantly greater frequency of STCL in BD than in healthy and disease controls. All but peptide 154-172 stimulated o nly the CD4+ subset of T cells, although there was no evidence that re activity to the selected peptides is restricted by DR2 to DR7 Ag. HLA- B51 is significantly associated with BD, but there was no evidence tha t B51 was a restricting element, when B51+ patients were compared with B51- patients with BD, and with B51+ healthy control subjects. A comp arative investigation was then carried out between the corresponding m ycobacterial and human HSP peptides. Similar or higher lymphoprolifera tive responses were stimulated by the human peptides compared with the mycobacterial peptides. These results suggest that the four peptide d eterminants within the 65-kDa HSP might be involved in the pathogenesi s of BD. Whereas the high microbial load and associated stress protein s found in oral ulceration of BD may initiate an immune response to th ese conserved epitopes, expression of autoreactive T cell clones might be stimulated by immunodominant T cell epitopes of endogenous HSP whi ch may induce immunopathologic changes.