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

TY - JOUR

T1 - Longer peptide can be accommodated in the MHC class I binding site by a protrusion mechanism

AU - Stryhn, A

AU - Pedersen, L O

AU - Holm, A

AU - Buus, S

N1 - Keywords: Amino Acid Sequence; Antigen Presentation; CD8-Positive T-Lymphocytes; Histocompatibility Antigens Class I; Humans; Molecular Sequence Data; Peptides; Tumor Cells, Cultured

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 11093123

SN - 0014-2980

VL - 30

SP - 3089

EP - 3099

JO - European Journal of Immunology

JF - European Journal of Immunology

IS - 11

ER -