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

Eur J Immunol. 2000 Nov;30(11):3089-99. doi: 10.1002/1521-4141(200011)30:11<3089::AID-IMMU3089>3.0.CO;2-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigen Presentation*
  • CD8-Positive T-Lymphocytes / immunology*
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Molecular Sequence Data
  • Peptides / immunology*
  • Tumor Cells, Cultured

Substances

  • Histocompatibility Antigens Class I
  • Peptides