Heat shock protein 70 moderately enhances peptide binding and transport by the transporter associated with antigen processing.
Hsp70 molecules are capable of binding antigenic peptides and eliciting CTL responses to the bound peptide. However, the precise mechanism for the induction of CTL has not been determined. One possibility is that hsp molecules can directly shuttle peptides in the MHC class I antigen processing and presentation pathway, as previously postulated. Here, we have addressed this issue by testing the effect of purified hsp70 molecules on peptide binding and transport by the transporter associated with antigen processing (TAP). Our results indicate that purified hsp70 molecules moderately enhance TAP function. In addition, we detect a physical association between hsp70 molecules and TAP, as well as the homologous drug transporter P-glycoprotein. We conclude that while hsp70 molecules may not be directly involved in the delivery of peptide to TAP, they may play an important role in TAP transport by binding to TAP and promoting its function.
Chen
D
D
Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, MRC-MOLONC, 12902 Magnolia Drive, Tampa, FL 33612, USA.
Androlewicz
M J
MJ
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000276:immunology* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001693:Biological Transport, Active / Q000187:drug effects; D002460:Cell Line; D018840:HSP70 Heat-Shock Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D018840:HSP70 Heat-Shock Proteins; D009842:Oligopeptides; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse