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PMID: 1379172 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

pH dependence and exchange of high and low responder peptides binding to a class II MHC molecule.

The EMBO journal ·Vol. 11 ·No. 8 ·1992-08-00 ·Pages 2829-39

Reay PA, Wettstein DA, Davis MM

Abstract

We have compared the binding kinetics of two antigenic peptides to a soluble class II MHC molecule. One of the peptides provokes a strong T cell response and the other a much weaker one. Both show greatly increased (approximately 40-fold) association rates at pH 5 in comparison to neutral pH, consistent with the low pH environment of late endosomes being most conducive to class II MHC--peptide binding. Interestingly, the weak peptide has a much faster off-rate that is significantly increased at pH 5 and it can be entirely replaced in an exchange reaction by the stronger one. This suggests that one characteristic of immunodominant peptides is that of nearly irreversible binding, such that they will be strongly selected for in the course of class II MHC transit and recycling through endosomal compartments. Modelling the parameters of this peptide exchange also suggests that a large fraction of the GPI-chimeric MHC molecules used in this study are 'empty' with respect to endogenous peptides, or else occupied with extremely weak ones, consistent with their inability to load processed peptides intracellularly.

MeSH Terms
Amino Acid Sequence Animals Cell Line Chimera Enzyme-Linked Immunosorbent Assay Epitopes/metabolism Histocompatibility Antigens Class II/metabolism Hydrogen-Ion Concentration Immune Sera Kinetics Molecular Sequence Data Peptides/chemical synthesis,immunology Type C Phospholipases/metabolism
Chemicals
Epitopes Histocompatibility Antigens Class II Immune Sera Peptides Type C Phospholipases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Reay P A
Howard Hughes Medical Institute, Stanford, CA.
Wettstein D A
Davis M M
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1992-08-00
Pages
2829-39
Language
English
Region
England
NLM ID
8208664
PMCID
PMC556762
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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