Can one predict antigenic peptides for MHC class I-restricted cytotoxic T lymphocytes useful for vaccination?
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-2Kb and H-2Db molecules, respectively. The HEL peptide HEL(70-78) was found to be able to induce HEL-specific CTL in H-2b mice also. Moreover, using an empiricial approach, we have also characterized the N-terminal HEL(1-17) peptide as an immunodominant antigenic peptide in the H-2k haplotype. This peptide presented by H-2Kk molecules neither contained the corresponding allele-specific binding motif nor fitted the expected 8-10 residue length.(ABSTRACT TRUNCATED AT 250 WORDS)
Calin-Laurens
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V
Immunobiologie moléculaire, UMR 49, CNRS-ENS-Lyon, France.
Trescol-Biémont
M C
MC
Gerlier
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D
Rabourdin-Combe
C
C
D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005240:Feasibility Studies; D006183:H-2 Antigens / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D009113:Muramidase / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D014612:Vaccines
D000939:Epitopes; D006183:H-2 Antigens; C024755:H-2K(K) antigen; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D014612:Vaccines; D009113:Muramidase