Effects of pH and polysaccharides on peptide binding to class II major histocompatibility complex molecules

Clifford V. Harding, Richard W. Roof, Paul M. Allen, Emil R. Unanue

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

The binding of immunogenic peptides to class II major histocompatibility molecules was examined at various pH values. We studied binding of peptides containing residues 52-61 from hen egg lysozyme (HEL) to I-Ak on fixed peritoneal macrophages or to solubilized affinity-purified I-Ak. Optimum binding occurred at pH 5.5-6.0 with accelerated kinetics relative to pH 7.4; equilibrium binding was also higher at pH 5.5-6.0 than at 7.4. Similar enhancement at pH 5-6 was observed for the binding of hemoglobin-(64-76) to I-Ek and of ribonuclease-(41-61) to I-Ak. In contrast, the binding of HEL-(34-45) to I-Ak was minimally enhanced at acid pH. Dissociation of cell-associated or purified peptide-I-Ak complexes was minimal between pH 5.5 and 7.4, with increased dissociation only at or below pH 4.0 [HEL-(46-61)] or pH 5.0 [HEL-(34-45)]. Thus, optimum peptide binding occurs at pH values similar to the endosomal environment, where the complexes appear to be formed during antigen processing. In addition, we examined the effect of a number of polysaccharides on the binding of peptide to I-Ak. None of these competed with the HEL peptide 125I-labeled YE52-61 for binding to I-Ak. [3H]Dextran also failed to bind purified I-Ak. Polysaccharides do not appear to bind to class II major histocompatibility complex molecules, which explains the T-cell independence of polysaccharide antigens.

Original languageEnglish
Pages (from-to)2740-2744
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number7
DOIs
StatePublished - Apr 1 1991

Fingerprint

Dive into the research topics of 'Effects of pH and polysaccharides on peptide binding to class II major histocompatibility complex molecules'. Together they form a unique fingerprint.

Cite this