By expressing TCR and pMHC on the surface of S. cerevisiae MATa and MATalpha haploid cells, the Yeast Agglutination Mediated TCR antigen Discovery system (YAMTAD) was designed and demonstrated to allow fast and unbiased library-on-library screening of TCR-pMHC interactions. The sequence of enriched peptide mutants and the TCR-CDR3 mutants can be identified using NGS.