Functional segregation of the TCR and antigen-MHC complexes on the surface of CTL.
As CTL adhere to and lyze their targets, they extract cognate Ag-MHC and represent this on their own cell surface. Whether such self-presented cognate Ag stimulate the TCR of a CTL is uncertain. To analyze this, we examined TCR capping in response to self-presented Ag. We found that OVA peptide-specific OT-1 CTL that were pulsed with cognate peptide Ag did not cap their TCR, implying that the autologously presented MHC-Ag complex does not normally stimulate the TCR. However, this functional separation of the TCR and its ligand on the cell surface was not absolute. Treatment of Ag-pulsed OT-1 CTL with agents that alter cell surface charge, including trypsin, papain, tunicamycin, neuraminidase, and polybrene, allowed Ag-specific TCR capping. The TCR capped together with the restricting MHC molecule on the surface of the cell, implying an interaction between the TCR and cell-associated Ag. Further, the treated CTL underwent a time- and dose-dependent suicidal death that was both Fas- and perforin-dependent. Therefore, our results indicate that the association of the TCR with its MHC-peptide ligand on the surface of a CTL is normally proscribed by biophysical properties of the plasma membrane. Overcoming this restriction allows TCR stimulation and induces CTL effector functions and cell suicide.
Mekala
Divya J
DJ
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Geiger
Terrence L
TL
D000818:Animals; D017951:Antigen Presentation; D016923:Cell Death / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D005110:Extracellular Space / Q000276:immunology; D006031:Glycosylation; D006183:H-2 Antigens / Q000378:metabolism / Q000502:physiology*; D007424:Intracellular Fluid / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D011940:Receptor Aggregation / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000648:ultrastructure; D014357:Trypsin / Q000494:pharmacology
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; C110366:OVA-8; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin; D014357:Trypsin