Numerous studies have focused on characterizing and monitoring antigen-specific T cells during the course of an immune response. Mostly indirect methods were used to circumvent the low frequency of T cell precursors and the inherent complexity of T cell receptor (TcR)-MHC-peptide interactions. Here, we took advantage of peptide-specific adhesion induced by immobilized MHC-peptide complexes. We describe a simple technique which allows enrichment in antigen-specific T lymphocytes among a heterogeneous CD8+ T cell population. Enrichment of T cells according to their specificity should facilitate their characterization and provide an attractive tool for immunotherapy.