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Updated: Oct 4, 2026
Peptide:MHC Tetramer-based Enrichment of Epitope-specific T cells
Published on: October 22, 2012
Efficient detection of human antigen-specific CD4+ T cells with peptide-exchangeable HLA-DP4 tetramers and
Shawn A Mahmud1, Grace D Frechette1, Lisa M Burzenski2
1Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, USA; Division of Pediatric Rheumatology, Allergy & Immunology, University of Minnesota Medical School, Minneapolis, MN, USA.
Abstract:
The tremendous variation in human MHCII alleles is a barrier to using fluorophore-labeled peptide:MHCII tetramers to study antigen-specific CD4+ T cells. This is because matching of the MHCII molecule in the tetramer with each human subject is required. We show that fluorophore-labeled tetramers of peptides complexed to the most common human MHCII molecule-encoded by DPA1*01:03 and DPB1*04:01-detect antigen-specific cells in most humans. New peptides can be successfully exchanged into these tetramers. Combining these novel exchangeable DP4 tetramers with a multiplexed magnetic enrichment step allows the detection of antigen-specific CD4+ T cell responses in ≥60% of humans without forehand knowledge of HLA type making pilot experiments with new tetramers more practical and efficient. This system could be adopted by the field to study CD4+ T cell responses to multiple independent antigens or multiple epitopes within an antigen (i.e., as a system for epitope discovery).
