The Journal of Immunology, Vol 154, Issue 6 2939-2948, Copyright © 1995 by American Association of Immunologists

ARTICLES

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

A Ben-Nun, I Mendel, G Sappler and N Kerlero de Rosbo
Department of Cell Biology, Weizmann Institute of Science, Rehovo, Israel.

Mycobacterium tuberculosis (Mt), routinely used to promote the induction of autoimmune diseases, can also protect against their development. Recently, we demonstrated that purified protein derivative (PPD) is the major fraction of Mt that protects mice against the induction of experimental autoimmune encephalomyelitis (EAE). We have now ascribed the protective activity to a 12-kDa protein purified from PPD. Sequence identity between the first 17 amino acids of the 12-kDa PPD protein and the 10-kDa BCG-a protein of Mt suggested that these proteins are identical or closely related. However, in contrast to the 12-kDa PPD protein, 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 identical. The protective activity of the 12-kDa PPD protein correlated with its ability to stimulate PPD-specific T cells. The significance of this correlation is not clear and the mechanism of protection was not fully elucidated. However, N-terminal sequence identity between the 12-kDa PPD protein and the 10-kDa BCG-a protein, which shares 43% homology with GroES stress protein, suggested that the 12-kDa PPD protein may also belong to the bacterial heat-shock protein (hsp) family. Thus, by analogy with protection against arthritis or diabetes by hsp65, the mechanism of protection could be based on shared T cell epitopes with the target self Ag. However, the 12-kDa PPD protein did not stimulate encephalitogenic T lymphocytes. Effective protection against EAE by the 12-kDa PPD protein, in the absence of a stimulatory effect on encephalitogenic T lymphocytes, suggests a potential use for this protein in the therapy of autoimmune diseases.

This article has been cited by other articles:

				W. VAN EDEN, G. WICK, S. ALBANI, and I. COHEN Stress, Heat Shock Proteins, and Autoimmunity: How Immune Responses to Heat Shock Proteins Are to Be Used for the Control of Chronic Inflammatory Diseases Ann. N.Y. Acad. Sci., October 1, 2007; 1113(1): 217 - 237. [Abstract] [Full Text] [PDF]

				D. L. Sewell, E. K. Reinke, D. O. Co, L. H. Hogan, R. B. Fritz, M. Sandor, and Z. Fabry Infection with Mycobacterium bovis BCG Diverts Traffic of Myelin Oligodendroglial Glycoprotein Autoantigen-Specific T Cells Away from the Central Nervous System and Ameliorates Experimental Autoimmune Encephalomyelitis Clin. Vaccine Immunol., July 1, 2003; 10(4): 564 - 572. [Abstract] [Full Text] [PDF]

				I. Rosenkrands, K. Weldingh, P. Ravn, L. Brandt, P. Hojrup, P. B. Rasmussen, A. R. Coates, M. Singh, P. Mascagni, and P. Andersen Differential T-Cell Recognition of Native and Recombinant Mycobacterium tuberculosis GroES Infect. Immun., November 1, 1999; 67(11): 5552 - 5558. [Abstract] [Full Text] [PDF]

				M. Falcone and B. R. Bloom A T Helper Cell 2 (Th2) Immune Response against Non-self Antigens Modifies the Cytokine Profile of Autoimmune T Cells and Protects against Experimental Allergic Encephalomyelitis J. Exp. Med., March 3, 1997; 185(5): 901 - 908. [Abstract] [Full Text] [PDF]