Quantitation of lysozyme peptides bound to class II MHC molecules indicates very large differences in levels of presentation

Knowing the abundance of peptides presented by MHC molecules is a crucial a spect for understanding T cell activation and tolerance. In this report we determined the relative abundance of four distinct peptide families after t he processing of the model Ag hen egg-white lysozyme. The development of a sensitive immunochemical approach reported here made it possible to directl y quantitate the abundance of these four epitopes presented by APCs, both i n vitro and in vivo. We observed a wide range of presentation among these f our different epitopes presented on the surface of APCs, with 250-fold diff erences or more between the most abundant epitope (48-63) and the least abu ndant epitopes. Importantly, we observe similar ratios of presentation from APCs in vitro as well as from APCs from the spleens and thymi of hen egg-w hite lysozyme transgenic mice. We discuss the relationship between the amou nt of peptide presented and their binding to I-A(k) molecules, immunogenici ty, and tolerogenicity.