MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I ALLELE-SPECIFIC PEPTIDE LIBRARIES - IDENTIFICATION OF PEPTIDES THAT MIMIC AN H-Y T-CELL EPITOPE

We describe a novel method for screening large libraries of random peptides for T cell antigens. Two libraries were constructed, containing fixed amino acids representing the major histocompatibility complex (MHC) class I anchor residues for H-2K(b)-restricted octamers and H-2D(b)-restricted nonamers. Peptides from the Kb-restricted library (K(b)L: SXIXFXXL) and the D-b-restricted library (D(b)L: XXXXNXXX(M)(I)) specifically stabilize empty K-b and D-b molecules, respectively. The libraries contain peptides that mimic several H-2(b)-restricted cytotoxic T lymphocyte epitopes, and 21 mimotopes for a D-b-restricted H-Y epitope were isolated. A degenerate synthetic peptide of limited complexity containing the identified H-Y sequence motif was found to be similar to the natural H-Y epitope by reverse-phase high performance liquid chromatography analysis. This peptide is also capable of immunizing female mice against male splenocytes. Several applications for MHC-restricted peptide libraries are discussed.