TY - JOUR
T1 - More efficient peptide binding to MHC class II molecules during cathepsin B digestion of Ii than after Ii release
AU - Daibata, Masanori
AU - Xu, Minzhen
AU - Humphreys, Robert E.
AU - Reyes, Victor E.
N1 - Funding Information:
Acknowledgements--We thank Patricia J. Downe and Marion Bonin for the typing of this manuscript. This work was supported by grants IM-582 and JFRA-374 from the American Cancer Society to R.E.H. and V.E.R., respectively; grant AHA-from the American Heart Association to V.E.R., and grant AI 34043 from the National Institutes of Health to V.E.R.
PY - 1994/3
Y1 - 1994/3
N2 - The binding of a T cell-presented peptide to MHC class II α,β chains occurs as a concurrent process with the release of the associated invariant chain (Ii) by cathepsin B. Ii was digested by cathepsin B from solubilized, MHC class II α,β,Ii complexes in the presence of N-hydroxysuccinimidyl-4-azidobenzoate-conjugated, 125I-labeled, influenza virus matrix (18-29) peptide. The peptide was crosslinked where it became bound. This HLA-DR1-restricted peptide bound about three times more efficiently to class II α,β chains of DR 1- positive B cells when present during cathepsin B digestion of Ii than when added afterward, also at pH 5.0. Binding was competed by similarly DR-restricted peptides. Cathepsin D cleaved Ii but did not enhance peptide binding. However, a trace level of cathepsin D, added to the assay for peptide binding in the presence of cathepsin B, further enhanced peptide binding about three times. These experiments support an hypothesis for the staged release of Ii fragments by cathepsin D and cathepsin B, catalyzing at one point the insertion of a peptide into the antigen binding site formed by class II α and β chains.
AB - The binding of a T cell-presented peptide to MHC class II α,β chains occurs as a concurrent process with the release of the associated invariant chain (Ii) by cathepsin B. Ii was digested by cathepsin B from solubilized, MHC class II α,β,Ii complexes in the presence of N-hydroxysuccinimidyl-4-azidobenzoate-conjugated, 125I-labeled, influenza virus matrix (18-29) peptide. The peptide was crosslinked where it became bound. This HLA-DR1-restricted peptide bound about three times more efficiently to class II α,β chains of DR 1- positive B cells when present during cathepsin B digestion of Ii than when added afterward, also at pH 5.0. Binding was competed by similarly DR-restricted peptides. Cathepsin D cleaved Ii but did not enhance peptide binding. However, a trace level of cathepsin D, added to the assay for peptide binding in the presence of cathepsin B, further enhanced peptide binding about three times. These experiments support an hypothesis for the staged release of Ii fragments by cathepsin D and cathepsin B, catalyzing at one point the insertion of a peptide into the antigen binding site formed by class II α and β chains.
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U2 - 10.1016/0161-5890(94)90122-8
DO - 10.1016/0161-5890(94)90122-8
M3 - Article
C2 - 8139580
AN - SCOPUS:0028219119
SN - 0161-5890
VL - 31
SP - 255
EP - 260
JO - Molecular Immunology
JF - Molecular Immunology
IS - 4
ER -