Engineered T-cell receptor tetramers bind MHC-peptide complexes with high affinity

Nat Biotechnol. 2004 Nov;22(11):1429-34. doi: 10.1038/nbt1024. Epub 2004 Oct 24.


In this study we extend tetramerization technology to T-cell receptors (TCRs). We identified TCR alpha beta pairs in the absence of accessory molecules, ensuring isolation of high-affinity TCRs that maintain stable binding characteristics after tetramerization. Subtle changes in cognate peptide levels bound to the class I molecule were accurately reflected by parallel changes in the mean fluorescence intensity of cells that bound TCR tetramers, allowing us to accurately assess the binding affinity of a panel of peptides to major histocompatibility complex (MHC) class I. Using a TCR tetramer specific for the Mamu-A(*)01 allele, we identified animals expressing this restricting class I allele from a large cohort of outbred rhesus macaques. TCR tetramers should facilitate analysis of the MHC-peptide interface and, more generally, the design of immunotherapeutics and vaccines.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen-Antibody Complex / analysis
  • Antigen-Antibody Reactions / immunology
  • Cells, Cultured
  • Dimerization
  • Fluorescence Polarization Immunoassay / methods*
  • Genes, MHC Class I / genetics
  • Genes, MHC Class I / immunology*
  • Macaca mulatta
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / immunology
  • Protein Binding
  • Protein Engineering / methods*
  • Protein Interaction Mapping / methods*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • T-Lymphocytes / immunology*


  • Antigen-Antibody Complex
  • Multiprotein Complexes
  • Receptors, Antigen, T-Cell, alpha-beta