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.

Figure 1. Dissociation curves of four HLA-A*02:01 complexes with different half-lifes ranging from 27.5 h to 0.2 h
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.

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.
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. Eur. J. Immunol. 2012. 42: 1405–1416
  2. J. Immunol. 2007 Jun 15;178(12):7890-901