Turnover of Ia-peptide complexes is facilitated in viable antigen-presenting cells: biosynthetic turnover of Ia vs. peptide exchange.
Macrophages and B cells process antigens to produce antigenic peptides that associate with class II major histocompatibility complex molecules (e.g., Ia molecules); these Ia-peptide complexes are recognized by CD4+ T lymphocytes. Processing of the antigen hen egg white lysozyme was inhibited by cycloheximide in peritoneal exudate cells (PECs, largely macrophages), but not in TA3 B-lymphoma cells. The uptake and metabolism of hen egg white lysozyme was largely intact in cycloheximide-treated PECs, implicating a blockade in other steps in the formation of Ia-peptide complexes. Turnover of Ia-peptide complexes was markedly enhanced in viable antigen-presenting cells (TA3 and PEC) as compared to such complexes studied on fixed cells or in isolated preparations of Ia and peptide. In B cells the half-life of Ia-peptide complexes was much shorter than the half-life of the Ia molecules, implying turnover of Ia-peptide complexes by dissociatin and peptide exchange. In PECs, the dissociation of Ia-peptide complexes was more limited; the enhanced Ia-peptide turnover in viable PECs reflected in part biosynthetic turnover of Ia molecules. Specific mechanisms may exist in TA3 cells to facilitate exchange of peptides bound to Ia, allowing recycling of Ia to present another antigenic peptide; such Ia recycling would explain the ability of these cells to process and present antigen in the absence of Ia synthesis.
Harding
C V
CV
Department of Pathology, Washington University School of Medicine, Saint Louis, MO 63110.
Roof
R W
RW
Unanue
E R
ER
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007700:Kinetics; D008223:Lymphoma; D051379:Mice; D010455:Peptides / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D010455:Peptides; D003513:Cycloheximide