MHC Monomers and Tetramers

pMHC STABILITY

Assessment of peptide-MHC complex stability is an important parameter when screening for immnunogenic peptides. The stability of any given peptide-MHC complex can be determined by monitoring the dissociation of immune complexes at 37°C and calculate the half-life. The half-life of a peptide-MHC complex have been demonstrated to be a better correlate of immunogenicity than the corresponding peptide affinity for the MHC (Harndahl et.al1).

We have developed a high-throughput assay to monitor the dissociation of peptide MHC class I complexes (figure 1) and determine the half-life of any peptide. Our stability measurement service applies to all MHC class I molecules available.

immunogenicity immunogen antigen-MHC stability A*02:01 CD8+ T cells neo-epitope screening
Figure 1. Dissociation curves of four HLA-A*02:01 complexes with different half-lifes ranging from 27.5 h to 0.2 h

The determination of the half-life of a set of peptides (pairwise matched for HLA-A*02:01 affinity) previously described as being either immunogenic or non-immunogenic (Assarsson E, et. al2) revealed that verified T cell epitopes produced significantly longer half-lives compared to verified non-immunogenic peptides (figure 2). A ROC analysis of the half-lives in the two groups produced an AUC of 0.97 suggesting that stability is a key parameter for immunogenicity assessments.

peptide MHC stability immunogenicity CD8+ T cells immunogenicity
Figure 2. Half-lives of peptide HLA-A*02:01 complexes previously described to be Immunogenic (T cell epitopes) or Non-Immunogenic. Error bars indicate mean with 95% CI.

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Bibliography

  1. Harndahl, M., M. Rasmussen, G. Roder, I. Dalgaard Pedersen, M. Sorensen, M. Nielsen and S. Buus (2012). “Peptide-MHC class I stability is a better predictor than peptide affinity of CTL immunogenicity.” Eur J Immunol 42(6): 1405-1416.
  2. Assarsson E1, Sidney J, Oseroff C, Pasquetto V, Bui HH, Frahm N, Brander C, Peters B, Grey H, Sette A. “A quantitative analysis of the variables affecting the repertoire of T cell specificities recognized after vaccinia virus infection.” J Immunol. 2007 Jun 15;178(12):7890-901.