Research ArticleT CELLS

High-throughput peptide-MHC complex generation and kinetic screenings of TCRs with peptide-receptive HLA-A*02:01 molecules

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Science Immunology  19 Jul 2019:
Vol. 4, Issue 37, eaav0860
DOI: 10.1126/sciimmunol.aav0860

Empty MHC reagents improve T cell detection

Recombinant MHC molecules displaying single peptides in their peptide binding cleft are valuable reagents for identifying T cells that bind specific peptide-MHC complexes. Two studies in this week’s issue show that disulfide-stabilized (DS) MHC class I molecules offer a more efficient path to preparing large libraries of MHC-peptide reagents. Saini et al. developed DS versions of three MHC class I molecules and used a library of DS HLA-A2–peptide multimers to rapidly screen T cells infiltrating human melanoma tumors for neoantigen reactivity. Moritz et al. prepared libraries of DS HLA-A2–peptide complexes to screen an affinity-matured TCR for cross-reactivity with self-peptide–MHC complexes. Empty MHC class I molecules that are stable and easily loaded with peptide will facilitate the wider use of MHC-peptide reagents for T cell detection. See related Research Article by Saini et al. in this issue.

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