Functional segregation of the TCR and antigen-MHC complexes on the surface of CTL.
J Immunol
; 171(8): 4089-95, 2003 Oct 15.
Article
in En
| MEDLINE
| ID: mdl-14530330
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptor Aggregation
/
Receptors, Antigen, T-Cell
/
T-Lymphocytes, Cytotoxic
/
H-2 Antigens
/
Antigen Presentation
Limits:
Animals
Language:
En
Journal:
J Immunol
Year:
2003
Document type:
Article
Affiliation country:
United States