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A flexible MHC class I multimer loading system for large-scale detection of antigen-specific T cells

Adaptive immunity is initiated by T cell recognition of specific antigens presented by major histocompatibility complexes (MHCs). MHC multimer technology has been developed for the detection, isolation, and characterization of T cells in infection, autoimmunity, and cancer. Here, we present a simple...

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Bibliographic Details
Published in:The Journal of experimental medicine 2018-05, Vol.215 (5), p.1493-1504
Main Authors: Luimstra, Jolien J, Garstka, Malgorzata A, Roex, Marthe C J, Redeker, Anke, Janssen, George M C, van Veelen, Peter A, Arens, Ramon, Falkenburg, J H Frederik, Neefjes, Jacques, Ovaa, Huib
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Language:English
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Summary:Adaptive immunity is initiated by T cell recognition of specific antigens presented by major histocompatibility complexes (MHCs). MHC multimer technology has been developed for the detection, isolation, and characterization of T cells in infection, autoimmunity, and cancer. Here, we present a simple, fast, flexible, and efficient method to generate many different MHC class I (MHC I) multimers in parallel using temperature-mediated peptide exchange. We designed conditional peptides for HLA-A*02:01 and H-2K that form stable peptide-MHC I complexes at low temperatures, but dissociate when exposed to a defined elevated temperature. The resulting conditional MHC I complexes, either alone or prepared as ready-to-use multimers, can swiftly be loaded with peptides of choice without additional handling and within a short time frame. We demonstrate the ease and flexibility of this approach by monitoring the antiviral immune constitution in an allogeneic stem cell transplant recipient and by analyzing CD8 T cell responses to viral epitopes in mice infected with lymphocytic choriomeningitis virus or cytomegalovirus.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20180156