Proteolytic cleavage of type I collagen generates an autoantigen in autoimmune uveitis.

Abstract

This study was initiated to induce experimental autoimmune anterior uveitis (EAAU) in Lewis rats by melanin-associated antigen (MAA; 22-kDa fragment of type I collagen alpha2 chain) derived from rat iris and ciliary body (CB), to localize MAA within the eye, and to investigate the possible mechanism of MAA generation in vivo. The EAAU model replicates idiopathic human anterior uveitis. Lewis rats sensitized to rat MAA developed anterior uveitis, and EAAU induced by rat MAA can be adoptively transferred to naive syngenic rats by MAA-primed T cells. Animals immunized with rat MAA developed cellular immunity to the antigen. MAA was detected only in the iris and CB of the eye. Iris and CB were the major source of matrix metalloproteinase-1 (MMP-1) in the naive eye, and ocular expression of MMP-1 was up-regulated, whereas expression of tissue inhibitor of metalloproteinase 1 decreased before the onset of EAAU. These results demonstrated that EAAU can be induced by autologous MAA. Uveitogenic antigen is present only in the iris and CB of the eye, and the imbalance between MMP-1 and tissue inhibitor of metalloproteinase 1 may play a role in the generation of MAA in vivo. Collectively, the evidence presented here suggests that MAA is an autoantigen in EAAU. These observations may extend to idiopathic human anterior uveitis and facilitate the development of antigen-specific therapy.

• Authors: Purushottam Jha, Balasubramanian Manickam, Bharati Matta, Puran S Bora, Nalini S Bora
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 284 Issue 45 Pg. 31401-11 (Nov 06 2009) ISSN: 1083-351X [Electronic] United States
• PMID: 19755419 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantigens
• Collagen Type I
• melanin-associated antigen, rat

Topics

• Animals
• Autoantigens (immunology, metabolism)
• Autoimmune Diseases (immunology, metabolism)
• Cattle
• Collagen Type I (immunology, metabolism)
• Disease Models, Animal
• Humans
• Male
• Protein Processing, Post-Translational
• Rats
• Rats, Inbred Lew
• Specific Pathogen-Free Organisms
• Uveitis, Anterior (immunology, metabolism)