Disparate binding of chaperone proteins by HLA-A subtypes.
We examined chaperone association with subtypes of HLA-A68 differing at positions 116 and/or 70, and analyzed the surface expression of each A68 subtype. Our findings with A68 indicate that certain subtypes have inefficient association with the assembly complex and correspondingly high surface expression, dependent on the character of position 116. Specifically, poor association of A68 subtypes with the transporter associated with antigen processing correlated with a comparatively high level of W6/32(+) forms at the cell surface. This observation suggests that intracellular retention is a dominant function of the assembly complex and that natural differences in assembly complex interaction may dictate the level of surface expression of MHC class I molecules. We also found that position 116 was crucial for HLA-A68 subtype association with the assembly complex. Our data contrast with results we obtained previously with HLA-B7 in that an aspartic acid at position 116 abrogated chaperone association for HLA-A68, whereas it increased association for HLA-B7. In total, HLA-A molecules exhibit natural allele-specific distinctions in chaperone association that correlate with differences in cell surface expression and with the identity of amino acid position 116.
Turnquist
Héth R
HR
Eppley Institute for Research in Cancer and Allied Diseases, Department of Pathology and Microbiology, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198-6805 USA.
Schenk
Erin L
EL
McIlhaney
Mary M
MM
Hickman
Heather D
HD
Hildebrand
William H
WH
Solheim
Joyce C
JC
D017920:Antiporters / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D005434:Flow Cytometry; D005973:Glutamine / Q000378:metabolism; D015234:HLA-A Antigens / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D026901:Membrane Transport Proteins; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014162:Transfection
D017920:Antiporters; D015234:HLA-A Antigens; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; C107762:tapasin; D005973:Glutamine; D001224:Aspartic Acid; D006639:Histidine