Soluble HLA proteins with bound peptides are released from the cell surface by the membrane metalloproteinase.
The metalloproteinase (MPase)-mediated pathway of MHC class I processing is a distinct cellular mechanism that generates soluble HLA proteins. It has been implicated in modulation of immune responses induced during transplantation events. It is, therefore, important to define the characteristics of soluble HLA species produced by the MPase pathway. We have previously shown that some mutant peptide-conformed beta(2)-microglobulin (beta(2)m) free heavy chains (HC) with lower affinity for beta(2)m can be released into supernatants by the MPase. These soluble conformed beta(2)m-free HC intermediates can re-associate with beta(2)m in solution giving rise to beta(2)m-associated HC. We now demonstrate that also nonmutant soluble conformed beta(2)m-free HC can be detected in supernatants of activated cells. These soluble HC intermediates appear to have bound peptides and readily re-associate with exogenous beta(2)m producing beta(2)m-associated HC that are stable at physiologic temperature. Thus, generation of peptide-conformed beta(2)m-free HC intermediates is an important step, which precedes generation of both soluble beta(2)m-free and beta(2)m-associated HC by the MPase pathway operating in activated cells.
Demaria
S
S
Laboratory of Molecular Immunology, Public Health Research Institute, New York, NY 10016, USA.
Bushkin
Y
Y
D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells; D006680:HLA Antigens / Q000737:chemistry / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015458:Leukemia, T-Cell / Q000201:enzymology / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D012995:Solubility; D012996:Solutions; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000378:metabolism
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D010455:Peptides; D012996:Solutions; D001613:beta 2-Microglobulin; D008666:Metalloendopeptidases