HLA-DR4-RESTRICTED T-CELL EPITOPES FROM THE MYCOBACTERIAL 60000 MW HEAT-SHOCK-PROTEIN (HSP-60) DO NOT MAP TO THE SEQUENCE HOMOLOGY REGIONS WITH THE HUMAN HSP-60

The mycobacterial 60 000 MW heat shock protein (hsp 60) is a major ant igen recognized by mycobacteria-reactive human CD4(+) T cells with lym phokine profiles and effector functions consistent with protective imm unity. In addition, the presence of a large number of T-cell epitopes presented by several HLA class II molecules makes this antigen relevan t to subunit vaccine design. However, the results from animal models a s well as human studies suggest that the mycobacterial hsp 60 may indu ce T-cell-mediated autoimmune conditions. In humans, the expression of HLA-DR4 represents a risk factor for some autoimmune diseases. These observations suggest that the epitopes from the mycobacterial hsp 60 p resented to T cells in the context of HLA-DR4 could be relevant to aut oimmunity. This is the first report on identification of HLA-DR4-restr icted T-cell epitopes from the mycobacterial antigen hsp 60. In total, five epitopes recognized in the context of HLA-DR4 by the M. leprae h sp 60-reactive CD4(+) T-cell clones from a subject immunized with M. l eprae were defined by synthetic peptides. Two of the epitopes were M. leprae-specific (aa 343-355, aa 522-534), whereas three epitopes were common to M. leprae and M. tuberculosis (aa 331-345, aa 441-455, aa 50 1-515). However, all of these epitopes belong to the regions that are highly divergent between the mycobacterial hsp60 and the homologous hu man hsp60 sequence, suggesting that the T cells recognizing the mycoba cterial hsp 60 in the context of HLA-DR4 may not necessarily induce au toreactivity.