Monoclonal antibodies specific for the empty conformation of HLA-DR1 reveal aspects of the conformational change associated with peptide binding

被引:42
|
作者
Carven, GJ
Chitta, S
Hilgert, I
Rushe, MM
Baggio, RF
Palmer, M
Arenas, JE
Strominger, JL
Horejsi, V
Santambrogio, L
Stern, LJ
机构
[1] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA
[2] MIT, Dept Chem, Cambridge, MA 02139 USA
[3] Acad Sci Czech Republ, Inst Genet Mol, CZ-16637 Prague, Czech Republic
[4] Appl Biosyst Cell Biol & Funct Proteom, Bedford, MA 01730 USA
[5] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA
[6] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA
[7] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA
关键词
D O I
10.1074/jbc.M314315200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Class II major histocompatibility complex (MHC) proteins bind peptides and present them at the cell surface for interaction with CD4(+) T cells as part of the system by which the immune system surveys the body for signs of infection. Peptide binding is known to induce conformational changes in class II MHC proteins on the basis of a variety of hydrodynamic and spectroscopic approaches, but the changes have not been clearly localized within the overall class II MHC structure. To map the peptide-induced conformational change for HLA-DR1, a common human class II MHC variant, we generated a series of monoclonal antibodies recognizing the beta subunit that are specific for the empty conformation. Each antibody reacted with the empty but not the peptide-loaded form, for both soluble recombinant protein and native protein expressed at the cell surface. Antibody binding epitopes were characterized using overlapping peptides and alanine scanning substitutions and were localized to two distinct regions of the protein. The pattern of key residues within the epitopes suggested that the two epitope regions undergo substantial conformational alteration during peptide binding. These results illuminate aspects of the structure of the empty forms and the nature of the peptide-induced conformational change.
引用
收藏
页码:16561 / 16570
页数:10
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