Naturally processed peptides longer than nine amino acid residues bind to the class I MHC molecule HLA-A2.1 with high affinity and in different conformations

Ye Chen, John Sidney, Scott Southwood, Andrea L. Cox, Kazuyasu Sakaguchi, Robert A. Henderson, Ettore Appella, Donald F. Hunt, Alessandro Sette, Victor H. Engelhard

Research output: Contribution to journalArticlepeer-review

Abstract

An equilibrium binding assay was used to directly measure the relative affinities of naturally processed 9-mer, 10-mer, and 12-mer peptides for the human class I MHC molecule HLA-A2.1. The peptides exhibited a range of affinities with IC50 values of 11 to 214 nM. The mode of interaction between these peptides and HLA-A2.1 was examined using peptides in which Asp had been substituted for suspected anchor residues. Regardless of length, the previously identified Leu at position 2 relative to the amino terminus was critical for peptide binding. While the carboxyl terminal residue was also critical for the binding of a 9-mer peptide, it was much less important in the binding of longer peptides. Additional residues close to the carboxyl terminus that contained aliphatic hydrocarbon side chains were of similar or greater importance in peptide binding. In addition, residue at position 3 also appeared to be important for the binding of longer peptides. The data suggest that different naturally occurring longer peptides can bind in different conformations to class I MHC molecules. While one of these is similar to the kinked conformation described by others, another conformation would involve an extension of the carboxyl terminus out of the class I binding site. The ability of MHC molecules to accommodate the same peptide in different conformations would appear to have distinct advantages to the immune system.

Original languageEnglish (US)
Pages (from-to)2874-2881
Number of pages8
JournalJournal of Immunology
Volume152
Issue number6
StatePublished - Mar 15 1994
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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