Poor correspondence between predicted and experimental binding of peptides to class I MHC molecules

Abstract

Naturally processed peptides presented by class I major histocompatibility complex (MHC) molecules display a characteristic allele specific motif of two or more essential amino acid side chains, the so-called peptide anchor residues, in the context of an 8-10 amino acid long peptide. Knowledge of the peptide binding motif of individual class I MHC molecules permits the selection of potential peptide antigens from proteins of infectious organisms that could induce protective T-cell-mediated immunity. Several methods have been developed for the prediction of potential class I MHC binding peptides. One is based on a simple scanning for the presence of primary peptide anchor residues in the sequence of interest. A more sophisticated technology is the utilization of predictive computer algorithms. Here, we have analyzed the experimental binding of 84 peptides selected on the basis of the presence of peptide binding motifs for individual class I MHC molecules. The actual binding was compared with the results obtained when analyzing the same peptides by two well-known, publicly available computer algorithms. We conclude that there is no strong correlation between actual and predicted binding when using predictive computer algorithms. Furthermore, we found a high number of false-negatives when using a predictive algorithm compared to simple scanning for the presence of primary anchor residues. We conclude that the peptide binding assay remains an important step in the identification of cytotoxic T lymphocyte (CTL) epitopes which can not be substituted by predictive algorithms.

Identification of an HLA-A1 restricted CTL epitope from Mcl-1

“…3 In the present study, the amino-acid sequence of the Mcl-1 protein was screened for the most probable HLA-A1 nona-and decamer peptide epitopes, using the main HLA-A1-specific anchor residues. 4 peptides only bound HLA-A1 very weakly. Subsequently, we scrutinized PBL from HLA-A1 þ cancer patients of different origins by means of ELISPOT against the Mcl-1(177-185) peptide as described.…”

“…Omi/HtrA2, a serine protease that also reside in intermembrane mitochondrial space, can act in both ways. 4 Recently, Okada and co-workers 5 observed that serine protease inhibitors TLCK and TPCK prevented the z-VAD-fmk plus imatinib-induced necrosis-like programmed cell death (PCD) pathway. They further found that serine protease inhibitors alone failed to prevent imatinib-treated cells from death.…”

Identification of Novel Survivin-Derived CTL Epitopes with Different HLA-A-Restriction Profiles

“…The amino acid sequence of the survivin protein was screened for the most probable HLA-A2 11-mer peptide epitopes, using the main HLA-A2 specific anchor residues. 32 Six survivin deduced peptides were synthesized and examined for binding to HLA-A2. None of the peptides examined bound with similar high affinity as a known positive control epitope from Epstein-Barr virus BMLF280-288 peptide (GLCTLVAML) ( Table 4).…”

The antiapoptotic member of the Bcl-2 family Mcl-1 is a CTL target in cancer patients

“…9 ) and scrutinized PBL from HLA-A3 þ cancer patients of different origin for reactivity against these peptides, taking advantage of the ELISPOT assay. This method has previously been shown to be highly efficient for the identification of tumor-specific CTL in cancer patients.…”