Longer peptide can be accommodated in the MHC class I binding site by a protrusion mechanism

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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.
Original languageEnglish
JournalEuropean Journal of Immunology
Volume30
Issue number11
Pages (from-to)3089-99
Number of pages10
ISSN0014-2980
Publication statusPublished - 2000

Bibliographical note

Keywords: Amino Acid Sequence; Antigen Presentation; CD8-Positive T-Lymphocytes; Histocompatibility Antigens Class I; Humans; Molecular Sequence Data; Peptides; Tumor Cells, Cultured

ID: 9944436