Identification of two distinct properties of class II major histocompatibility complex-associated peptides

Christopher A. Nelson, Shirley J. Petzold, Emil R. Unanue

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We have examined the interactions of various peptides with the mouse class II major histocompatibility complex molecule I-Ak. The peptides were derived from the model protein hen egg white lysozyme (HEL). The immunodominant peptide of HEL is a 10-mer, residues 52-61. Our previous work established that this sequence contains the key residues for binding and presentation to T cells. Now we show that the binding of this 10-mer sequence resulted in complexes of I-Ak and peptide that, in SDS/PAGE (without boiling the protein), rapidly dissociated from the component α and β chains. The binding interactions were studied in vitro, by incubating purified I-Ak and radiolabeled peptide, or ex vivo, by using antigen-presenting cells incubated with peptides. Peptides with additional residues at either the amino or carboxyl terminus behaved dramatically differently. Complexes of I-Ak with the longer peptides were stable to SDS/PAGE. Very few amino acid additions result in the change from unstable to stable complexes. The important issue here is that when cultured with HEL, antigen-presenting cells selected the HEL peptides containing the 52-61 sequences that favored stability [Nelson, C. A., Roof, R. W., McCourt, D. W. & Unanue, E. R. (1992) Proc. Natl. Acad. Sci. USA 89, 7380-7383]. Also, from other studies, such sequences correlate with a high inununogenicity of the peptide. We conclude that there are structural features of peptides that change the stability of the class II molecule and that are independent of the "core" peptide seen by the T cells.

Original languageEnglish
Pages (from-to)1227-1231
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number4
StatePublished - Feb 15 1993


  • Antigen
  • Immunogenicity
  • Peptide binding
  • T cell


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