The set of peptides that is bound by a given major histocompatibility complex class I product can be described by one or two properly spaced anchor residues, and two properly spaced peptide termini, approximately 8-10 residues apart. Using radiolabeled peptide libraries, we examined whether mutations in those "pockets" in class I Kb molecules that do not seem critically involved in the interaction with the peptide anchor residues, do exert an effect on the set of preferred peptides. We find that mutations in all the pockets found in the structure of Kb have a significant effect on the peptide preference of the molecule, and their recognition by cytotoxic T cells. Alterations in substrate specificity are also observed for mutations involving residues that interact with main chain atoms in both peptide termini. These findings challenge a static view of the interaction of peptide termini with their respective pockets in the class I molecule, and imply a role for the minor pockets in peptide selectivity.
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1 June 1993
Article|
June 01 1993
Polymorphisms in pockets of major histocompatibility complex class I molecules influence peptide preference.
E M Rohren,
E M Rohren
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905.
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L R Pease,
L R Pease
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905.
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H L Ploegh,
H L Ploegh
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905.
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T N Schumacher
T N Schumacher
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905.
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E M Rohren
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905.
L R Pease
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905.
H L Ploegh
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905.
T N Schumacher
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1993) 177 (6): 1713–1721.
Citation
E M Rohren, L R Pease, H L Ploegh, T N Schumacher; Polymorphisms in pockets of major histocompatibility complex class I molecules influence peptide preference.. J Exp Med 1 June 1993; 177 (6): 1713–1721. doi: https://doi.org/10.1084/jem.177.6.1713
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