title: Longer peptide can be accommodated in the MHC class I binding site by a protrusion mechanism.
abstract: According to current consensus, CD8(+) T cell responses are focused upon short peptide sequences (8-11 amino acids) presented by MHC class I molecules. This size restriction is thought to operate mostly at the level of peptide-MHC class I interaction. Crystal structures have shown that the free N and C termini of a bound peptide interact through hydrogen bonding networks to conserved residues at either end of the class I binding site. Accordingly, it is thought that the termini are fixed and that only minor variations in peptide size are possible through a central bulging mechanism. We find that this consensus view is not always correct as some peptide-MHC class I interaction will accept significant extensions. Furthermore, our results indicate that in some cases protrusion, rather than bulging, may be the mechanism of extension. Depending upon the particular peptide-MHC combination in question, such extensions can occur at either the N or C terminus (but never both at the same time). Finally, we show that MHC and T cell in some cases can detect the identity of the extension, i.e. that extensions may be part of the specificity of the T cell immune response. We suggest that such extensions may play a physiological role.
authors.affiliation: Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark. A.Stryhn@immi.ku.dk
authors.forename: A
authors.initials: A
authors.lastname: Stryhn
authors.forename: L O
authors.initials: LO
authors.lastname: Pedersen
authors.forename: A
authors.initials: A
authors.lastname: Holm
authors.forename: S
authors.initials: S
authors.lastname: Buus
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides