Definition and transfer of a serological epitope specific for peptide-empty forms of MHC class I.
Nascent class I molecules have been hypothesized to undergo a conformational change when they bind peptide based on the observation that most available antibodies only detect peptide-loaded class I. Furthermore recent evidence suggests that this peptide-facilitated conformational change induces the release of class I from association with transporter associated with antigen processing (TAP)/tapasin and other endoplasmic reticulum proteins facilitating class I assembly. To learn more about the structure of peptide-empty class I, we have studied mAb 64-3-7 that is specific for peptide-empty forms of L(d). We show here that mAb 64-3-7 detects a linear stretch of amino acids including principally residues 48Q and 50P. Furthermore, we demonstrate that the 64-3-7 epitope can be transferred to other class I molecules with limited mutagenesis. Interestingly, in the folded class I molecule residues 48 and 50 are on a loop connecting a beta strand (under the bound peptide) with the alpha(1) helix (rising above the ligand binding site). Thus it is attractive to propose that this loop is a hinge region. Importantly, the three-dimensional structure of this loop is strikingly conserved among class I molecules. Thus our findings suggest that all class I molecules undergo a similar conformational change in the loop around residues 48 and 50 when they associate with peptide.
Yu
Y Y
YY
Department of Genetics, Washington University School of Medicine, St Louis, MO 63110, USA.
Myers
N B
NB
Hilbert
C M
CM
Harris
M R
MR
Balendiran
G K
GK
Hansen
T H
TH
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D000939:Epitopes; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015395:Histocompatibility Antigens Class I