Threshold for peptide selection (binding affinity) used to identify candidate T cell epitopes

Value 500 nM
Organism Mammals
Reference Paul S, Weiskopf D, Angelo MA, Sidney J, Peters B, Sette A. HLA class I alleles are associated with peptide-binding repertoires of different size, affinity, and immunogenicity. J Immunol. 2013 Dec 15 191(12):5831-9. doi: 10.4049/jimmunol.1302101 abstract, p.1 bottom paragraph & p.4 2nd paragraphPubMed ID24190657
Primary Source [5] Sette A et al., The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J Immunol. 1994 Dec 15 153(12):5586-92.PubMed ID7527444
Method Primary source abstract: "The relationship between binding affinity for HLA [human leukocyte antigen] class I molecules and immunogenicity of discrete peptide epitopes has been analyzed in two different experimental approaches. In the first approach, the immunogenicity of potential epitopes ranging in MHC [major histocompatibility complex] binding affinity over a 10,000-fold range was analyzed in HLA-A*0201 transgenic mice. In the second approach, the antigenicity of approximately 100 different hepatitis B virus (HBV)-derived potential epitopes, all carrying A*0201 binding motifs, was assessed by using PBL [Peripheral blood lymphocytes] of acute hepatitis patients. In both cases, it was found that an affinity threshold of approximately 500 nM (preferably 50 nM or less) apparently determines the capacity of a peptide epitope to elicit a CTL [cytotoxic T-lymphocyte] response." Primary source studied mice & humans
Comments Abstract: "Prediction of HLA binding affinity is widely used to identify candidate T cell epitopes, and an affinity of 500 nM is routinely used as a threshold for peptide selection. However, the fraction (percentage) of peptides predicted to bind with affinities of 500 nM varies by allele." P.1 bottom paragraph: "Previous studies indicated 500 nM as an MHC affinity threshold associated with potential immunogenicity for HLA class I restricted T cells (primary source)." p.4 2nd paragraph: "Previously, based on analyses undertaken in the context of HLA A*0201, it was noted that the majority of HLA class I restricted epitopes bound with an affinity of 500 nM (IC50 ≤ 500nM) or better (primary source). In the present study [investigators] sought to examine whether the number of peptides predicted to bind at this affinity threshold was fairly uniform, or whether different alleles were associated with different repertoire sizes." P.6 6th paragraph: "Despite these large variations, 500 nM is still a useful binding threshold. Overall, the median % fraction of epitopes identified by this threshold is 79%."
Entered by Uri M
ID 113840