Antigen-specific inhibition of high-avidity T cell target lysis by low-avidity T cells via trogocytosis.
Cell Rep
; 8(3): 871-882, 2014 Aug 07.
Article
in En
| MEDLINE
| ID: mdl-25088413
ABSTRACT
Current vaccine conditions predominantly elicit low-avidity cytotoxic T lymphocytes (CTLs), which are non-tumor-cytolytic but indistinguishable by tetramer staining or enzyme-linked immunospot from high-avidity CTLs. Using CTL clones of high or low avidity for melanoma antigens, we show that low-avidity CTLs can inhibit tumor lysis by high-avidity CTLs in an antigen-specific manner. This phenomenon operates in vivo high-avidity CTLs control tumor growth in animals but not in combination with low-avidity CTLs specific for the same antigen. The mechanism involves stripping of specific peptide-major histocompatibility complexes (pMHCs) via trogocytosis by low-avidity melanoma-specific CTLs without degranulation, leading to insufficient levels of specific pMHC on target cell surface to trigger lysis by high-avidity CTLs. As such, peptide repertoire on the cell surface is dynamic and continually shaped by interactions with T cells. These results describe immune regulation by low-avidity T cells and have implications for vaccine design.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes, Cytotoxic
/
HLA-A Antigens
/
Melanoma
/
Antibody Affinity
Limits:
Humans
Language:
En
Journal:
Cell Rep
Year:
2014
Document type:
Article
Affiliation country: