Formation of a highly peptide-receptive state of class II MHC.
Peptide binding to class II MHC proteins occurs in acidic endosomal compartments following dissociation of class II-associated invariant chain peptide (CLIP). Based on peptide binding both to empty class II MHC and to molecules preloaded with peptides including CLIP, we find evidence for two isomeric forms of empty MHC. One (inactive) does not bind peptide. The other (active) binds peptide rapidly, with k(on) 1000-fold faster than previous estimates. The active isomer can be formed either by slow isomerization of the inactive molecule or by dissociation of a preformed peptide/MHC complex. In the absence of peptide, the active isomer is unstable, rapidly converting to the inactive isomer. These results demonstrate that fast peptide binding is an inherent property of one isomer of empty class II MHC. Dissociation of peptides such as CLIP yields this transient, peptide-receptive isomer.
Rabinowitz
J D
JD
Department of Chemistry, Stanford University, California 94305, USA.
Vrljic
M
M
Kasson
P M
PM
Liang
M N
MN
Busch
R
R
Boniface
J J
JJ
Davis
M M
MM
McConnell
H M
HM
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D003574:Cytochrome c Group / Q000378:metabolism; D005326:Fetal Proteins / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D036122:Receptor, EphA4
D000941:Antigens; D000944:Antigens, Differentiation, B-Lymphocyte; D003574:Cytochrome c Group; D005326:Fetal Proteins; D000949:Histocompatibility Antigens Class II; D009842:Oligopeptides; D020033:Protein Isoforms; C045084:invariant chain; D020794:Receptor Protein-Tyrosine Kinases; D036122:Receptor, EphA4