Identification of CD8+T-Cell-Stimulating Antigen Genes in cDNA Libraries

Molecular identification of the major histocompatibility complex (MHC)-bound antigenic (Ag) peptides recognized by CD8⁺ T-cells has remained elusive until recently, because of the lack of a simple and efficient method to isolate these Ags (1 ). Each MHC-I molecule presents thousands of distinct peptides, only one of which is usually recognized by a given T-cell (2 ,3 ). This enormous complexity of the peptide pool presents a formidable challenge to the identification of the Ag peptide in complex Ags such as transplanted tissues and tumors. Here is described the expression-cloning method developed in this laboratory for the identification of the donor Ag gene that has been applied to the identification of histocompatibility Ags. This and similar methods have also been successful in the identification of CD8⁺ T-cell Ags in tumors, allogeneic cells, and in autoimmunity (4 -7 ).