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J. Biol. Chem., Vol. 277, Issue 1, 155-160, January 4, 2002
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From the Department of Biochemistry, Tulane University Health
Sciences Center, New Orleans, Louisiana 70112-2699
Antigen three-dimensional structure potentially
limits antigen processing and presentation to helper T-cell epitopes.
The association of helper T-cell epitopes with the mobile loop in Hsp10s from mycobacteria and bacteriophage T4 suggests that the mobile
loop facilitates proteolytic processing and presentation of adjacent
sequences. Sites of initial proteolytic cleavage were mapped in
divergent Hsp10s after treatment with a variety of proteases including
cathepsin S. Each protease preferentially cleaved the Hsp10s in the
mobile loop. Flexibility in the 22-residue mobile loop most probably
allows it to conform to protease active sites. Three variants of the
bacteriophage T4 Hsp10 were constructed with deletions in the mobile
loop to test the hypothesis that shorter loops would be less sensitive
to proteolysis. The two largest deletions effectively inhibited
proteolysis by several proteases. Circular dichroism spectra and
chemical cross-linking of the deletion variants indicate that the
secondary and quaternary structures of the variants are native-like,
and all three variants were more thermostable than the wild-type Hsp10.
Local structural flexibility appears to be a general requirement for
proteolytic sensitivity, and thus, it could be an important factor in
antigen processing and helper T-cell epitope immunogenicity.
Proteolytic Sensitivity and Helper T-cell Epitope Immunodominance
Associated with the Mobile Loop in Hsp10s*
*
This work was supported by National Institutes of Health
Grant R01-AI42350.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Biochemistry,
Tulane University Health Sciences Center, 1430 Tulane Ave., New
Orleans, LA 70112-2699. Tel.: 504-586-3990; Fax: 504-584-2739; E-mail: landry@tulane.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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