On the complexity of self

Abstract

SELF peptides bound to self major histocompatibility complex (MHC) molecules have been implicated both in positive^1,2 and in negative^3,4 selection of T cells during intrathymic development. We report here that the novel MHC-restricted monoclonal antibody Y-Ae (ref. 5) detects the MHC class II bound form of a major self peptide⁶. Y-Ae binds ∼12% of the relevant MHC class II molecules on self antigen presenting cells. The peptide detected by Y-Ae is one of several major peptides eluted from the MHC molecule⁶. These data suggest that self peptides presented by self MHC class II molecules at densities sufficient to signal a CD4 T cell are of very limited complexity. Furthermore, as Y-Ae stains antigen presenting cells that mediate negative selection but not thymic cortical epithelial cells⁵ that drive positive selection³, differential expression of self peptide:self MHC class II complexes may be a key feature of intrathymic selection.