Anti-peptide antibody blocks peptide binding to MHC class I molecules in the endoplasmic reticulum.
The finding that MHC class I molecules are physically associated with the TAP transporter has suggested that peptides may be directly transported into the binding groove of the class I molecules rather than into the lumen of the endoplasmic reticulum (ER) where they subsequently would encounter class I molecules by diffusion. Such a mechanism would protect peptides from peptidases in the ER and/or escaping back into the cytoplasm. However, we find that an anti-peptide Ab that is cotranslationally transported into the ER prevents TAP-transported peptides from being presented on class I molecules. The Ab only blocks the binding of its cognate peptide (SIINFEKL) but not other peptides (KVVRFKDL, ASNENMETM, and FAPGNYPAL). Therefore, most TAP-transported peptides must diffuse through the lumen of the ER before binding stably to MHC class I molecules.
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
C J
CJ
Hilton
A M
AM
Dahl
K L
KL
Rock
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D019138:Antibodies, Blocking / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D002460:Cell Line; D004058:Diffusion; D004527:Egg Proteins / Q000276:immunology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006183:H-2 Antigens / Q000378:metabolism*; D006825:Hybridomas; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018528:ATP-Binding Cassette Transporters; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D004527:Egg Proteins; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin