DEFINITION OF NATURAL T-CELL ANTIGENS WITH MIMICRY EPITOPES OBTAINED FROM DEDICATED SYNTHETIC PEPTIDE LIBRARIES

Progress has recently been made in the use of synthetic peptide librar ies for the identification of T cell-stimulating ligands. T cell epito pes identified from synthetic libraries are mimics of natural epitopes , Here we show how the mimicry epitopes obtained from synthetic peptid e libraries enable unambiguous identification of natural T cell Ags, S ynthetic peptide libraries were screened with Mycobacterium tuberculos is-reactive and -autoreactive T cell clones, In two cases, database ho mology searches with mimicry epitopes isolated from a dedicated synthe tic peptide library allowed immediate identification of the natural an tigenic protein. In two other eases, an amino acid pattern that reflec ted the epitope requirements of the T cell was determined by substitut ion and omission mixture analysis. Subsequently, the natural Ag was id entified from databases using this refined pattern, This approach open s new perspectives for rapid and reliable Ag definition, representing a feasible alternative to the biochemical and genetic approaches descr ibed thus far.