Can one predict antigenic peptides for MHC class I-restricted cytotoxic T lymphocytes useful for vaccination?

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The cytotoxic T-lymphocyte (CTL) response can be crucial for efficient immunological control of intracellular pathogens and the MHC class I-restricted CTL have a major role to play in this process. They recognize complexes associating antigen-derived peptides with MHC class I molecules expressed on infected target cells. The characterization of these antigenic peptides is thus a key issue for developing vaccines efficient in inducing specific CTL. Recently, by sequencing the whole set of self-peptides eluted from a given MHC class I molecule, Falk and colleagues have found that they have a homogeneous 8–10 residue length and contain allele-specific peptidic motifs with two conservative dominant anchor residues. The existence of consensus motifs opens the way for a strategy to predict the MHC class I-restricted T-cell epitopes and here we discuss such an approach using hen egg lysozyme (HEL) as an antigenic model. Two HEL peptides corresponding to allele-specific motifs were found, HEL(49–56) and HEL(70–78) peptides, which can associate with MHC class I H-2K b and H-2D b molecules, respectively. The HEL peptide HEL(70–78) was found to be able to induce HEL-specific CTL in H-2 b mice also. Moreover, using an empirical approach, we have also characterized the N-terminal HEL(1–17) peptide as an immunodominant antigenic peptide in the H-2 k haplotype. This peptide presented by H-2K k molecules neither contained the corresponding allele-specific binding motif nor fitted the expected 8–10 residue length. These and other recently reported data illustrate the validity and limitation of predicting antigenic peptides that can bind to MHC class I by looking for allele-specific peptidie motifs in an antigen peptide sequence.