RESISTANCE TO HERPES STROMAL KERATITIS CONFERRED BY AN IGG2A-DERIVED PEPTIDE

NOT all peripheral tissue antigens enter the thymus and it is unclear how the immune system remains tolerant to this class of self antigen. As tolerance to self peptides can generate gaps in the T-cell repertoi re for cross-reactive foreign antigens(1,2), we investigated whether t his mechanism might also diminish autoimmune reactions to similar pept ides expressed by peripheral tissues. Herpes stromal keratitis (HSK) i s a virally induced autoimmune reaction against corneal tissues mediat ed by T cells(3-5), and is a leading cause of human blindness(6). Resi stance to HSK in mice is associated with allotypic variation in immuno globulin genes(7,8), possibly because circulating immunoglobin-derived peptides can cross-tolerize T cells specific for corneal tissue autoa ntigens. Here we show that HSK is mediated by T-cell clones specific f or corneal self antigens which also recognize an allotype-bearing pept ide derived from IgG2a, and that exposure of HSK-susceptible mice to a soluble form of this peptide confers resistance to HSK. Shared expres sion of peptide subsequences between sequestered tissue proteins and c irculating proteins may be important for maintenance of self-tolerance and prevention of autoimmunity.