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

作者: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*
来源:Journal of Experimental Medicine, 2018, 215(5): 1493-1504.
DOI:10.1084/jem.20180156

摘要

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(b) 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.