Interactions of HLA-B27 with the peptide loading complex as revealed by heavy chain mutations.
MHC class I heavy chains assemble in the endoplasmic reticulum with beta(2)-microglobulin and peptide to form heterotrimers. Although full assembly is required for stable class I molecules to be expressed on the cell surface, class I alleles can differ significantly in their rates of, and dependencies on, full assembly. Furthermore, these differences can account for class I allele-specific disparities in antigen presentation to T cells. Recent studies suggest that class I assembly is assisted by an elaborate complex of proteins in the endoplasmic reticulum, collectively referred to as the peptide loading complex. In this report we take a mutagenesis approach to define how HLA-B27 molecules interact with the peptide loading complex. Our results define subtle differences between how B27 mutants interact with tapasin (TPN) and calreticulin (CRT) in comparison to similar mutations in other mouse and human class I molecules. Furthermore, these disparate interactions seen among class I molecules allow us to propose a spatial model by which all class I molecules interact with TPN and CRT, two molecular chaperones implicated in facilitating the binding of high-affinity peptide ligands.
Harris
M R
MR
Department of Genetics, Washington University School of Medicine, St Louis, MO 63110, USA.
Lybarger
L
L
Myers
N B
NB
Hilbert
C
C
Solheim
J C
JC
Hansen
T H
TH
Yu
Y Y
YY
D017920:Antiporters / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D037282:Calreticulin; D015796:HLA-B27 Antigen / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism*; D011134:Polysaccharides; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012261:Ribonucleoproteins / Q000378:metabolism*
D017920:Antiporters; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D015796:HLA-B27 Antigen; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; D011134:Polysaccharides; D012261:Ribonucleoproteins; C107762:tapasin