A 12-KDA PROTEIN OF MYCOBACTERIUM-TUBERCULOSIS PROTECTS MICE AGAINST EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS - PROTECTION IN THE ABSENCE OF SHARED T-CELL EPITOPES WITH ENCEPHALITOGENIC PROTEINS

Mycobacterium tuberculosis (Mt), routinely used to promote the inducti on of autoimmune diseases, can also protect against their development. Recently, we demonstrated that purified protein derivative (PPD) is t he major fraction of Mt that protects mice against the induction of ex perimental autoimmune encephalomyelitis (EAE). We have now ascribed th e protective activity to a 12-kDa protein purified from PPD. Sequence identity between the first 17 amino acids of the 12-kDa PPD protein an d the 10-kDa BCC-a protein of Mt suggested that these proteins are ide ntical or closely related. However, in contrast to the 12-kDa PPD prot ein, the 10-kDa BCG-a protein did not protect against EAE, nor did it stimulate PPD-specific T cells, suggesting that the 12-kDa PPD protein and the 10-kDa BCG-a protein share some homology but are not identica l. The protective activity of the 12-kDa PPD protein correlated with i ts ability to stimulate PPD-specific T cells. The significance of this correlation is not clear and the mechanism of protection was not full y elucidated. However, N-terminal sequence identity between the 12-kDa PPD protein and the 10-kDa BCG-a protein, which shares 43% homology w ith GroES stress protein, suggested that the 12-kDa PPD protein may al so belong to the bacterial heat-shock protein (hsp) family. Thus, by a nalogy with protection against arthritis or diabetes by hsp65, the mec hanism of protection could be based on shared T cell epitopes with the target self Ag. However, the 12-kDa PPD protein did not stimulate enc ephalitogenic T lymphocytes. Effective protection against EAE by the 1 2-kDa PPD protein, in the absence of a stimulatory effect on encephali togenic T lymphocytes, suggests a potential use for this protein in th e therapy of autoimmune diseases.