Adjuvant arthritis (AA) is a chronic autoimmune disease in rats induced by immunization with Mycobacterium tuberculosis antigens. Research has shown that AA is associated with T-cell recognition of a cross-reactive epitope between M. tuberculosis and self-antigens in joint cartilage. A critical epitope was identified in the 65K protein of Mycobacterium bovis BCG, specifically the amino acids 180–188. This epitope is recognized by T-cell clones A2b and A2c, which are involved in AA development and resistance. Administration of the 65K antigen induced resistance to AA, suggesting that it may promote the emergence of suppressor-inducer T cells (A2c). The 65K antigen is also recognized by T cells from patients with rheumatoid arthritis, indicating its potential as a target for T-cell recognition in autoimmune diseases. The study used recombinant mycobacterial antigens and synthetic peptides to map the epitope. T-cell clones A2b and A2c responded to the 65K protein and its truncated derivatives. Synthetic peptides corresponding to the 65K protein were tested, and the 180–188 sequence was identified as the critical epitope for both clones. This sequence showed some similarity to the link protein of rat proteoglycan, but not to the core protein of chicken and rat proteoglycan. The 65K antigen, when administered in oil, did not induce AA but protected rats from subsequent AA induction. This suggests that the 65K antigen may induce the development of suppressor-inducer T cells (A2c), which help in resistance to AA. The study also highlights the potential of the 65K antigen as a therapeutic target for autoimmune diseases, as it may induce therapeutic suppression of the disease process. The 65K protein is a heat-shock protein and may play a role in autoimmune arthritis due to its cross-reactivity with environmental bacteria. The study provides insights into the molecular mechanisms underlying AA and the role of T-cell epitopes in autoimmune diseases.Adjuvant arthritis (AA) is a chronic autoimmune disease in rats induced by immunization with Mycobacterium tuberculosis antigens. Research has shown that AA is associated with T-cell recognition of a cross-reactive epitope between M. tuberculosis and self-antigens in joint cartilage. A critical epitope was identified in the 65K protein of Mycobacterium bovis BCG, specifically the amino acids 180–188. This epitope is recognized by T-cell clones A2b and A2c, which are involved in AA development and resistance. Administration of the 65K antigen induced resistance to AA, suggesting that it may promote the emergence of suppressor-inducer T cells (A2c). The 65K antigen is also recognized by T cells from patients with rheumatoid arthritis, indicating its potential as a target for T-cell recognition in autoimmune diseases. The study used recombinant mycobacterial antigens and synthetic peptides to map the epitope. T-cell clones A2b and A2c responded to the 65K protein and its truncated derivatives. Synthetic peptides corresponding to the 65K protein were tested, and the 180–188 sequence was identified as the critical epitope for both clones. This sequence showed some similarity to the link protein of rat proteoglycan, but not to the core protein of chicken and rat proteoglycan. The 65K antigen, when administered in oil, did not induce AA but protected rats from subsequent AA induction. This suggests that the 65K antigen may induce the development of suppressor-inducer T cells (A2c), which help in resistance to AA. The study also highlights the potential of the 65K antigen as a therapeutic target for autoimmune diseases, as it may induce therapeutic suppression of the disease process. The 65K protein is a heat-shock protein and may play a role in autoimmune arthritis due to its cross-reactivity with environmental bacteria. The study provides insights into the molecular mechanisms underlying AA and the role of T-cell epitopes in autoimmune diseases.