Kasey October Model
Edel Dieringer
In our earlier studies using either mice tolerized or transgenic for the foreign Ag, hen egg white lysozyme (HEL)4 (7, 8), or mouse lysozyme (ML) as a model self-Ag (9), we observed that mice are tolerant to the native neoself/self-Ag but that the T cells directed against cryptic self-determinants exist in the mature repertoire. Furthermore, we proposed that the anticryptic T cell repertoire might be involved in the induction of autoimmunity (10). In this study, we have examined the physiological significance of both the hierarchy (dominance/crypticity) of determinants within self-lysozyme, ML, and the T cell repertoire potentially directed against cryptic determinants of ML. We determined the MHC binding of ML peptides spanning the entire length of native lysozyme and evaluated the results in relation to the immunogenicity of these peptides. We also tested whether foreign (HEL) antigenic determinants make an impact on priming and expansion of the anticryptic self-T cell repertoire. We specifically addressed two crucial questions using the ML system: 1) are nonimmunogenic regions within ML capable of binding to the MHC, and thereby do they represent potentially dominant self-determinants, which can lead to tolerance induction in the thymus in vivo, or are they nondeterminants, incapable of binding to the particular MHC of the mouse strains tested; and 2) can the foreign homologue of ML, HEL, prime and expand the T cell repertoire potentially directed against the cryptic determinants of self-lysozyme, ML, and vice versa?