INVESTIGADORES
ZWIRNER Norberto Walter
congresos y reuniones científicas
Título:
Active transfer and endocytosis of MICA (MHC class I related chain gene A) from the cell surface of melanomas to activated T lymphocytes
Autor/es:
DOMAICA, CAROLINA INÉS; FUERTES, MERCEDES BEATRIZ; GIRART, MARÍA VICTORIA; ROSSI, LUCAS EZEQUIEL; ZWIRNER, NORBERTO WALTER
Lugar:
Río de Janeiro, Brasil
Reunión:
Congreso; 13th International Congress of Immunology; 2007
Institución organizadora:
International Union of Immunology Societies
Resumen:
NK cells trigger cytotoxicity against tumors using receptors such as NKG2D. NKG2D recognizes several ligands (NKG2DL) such as some transmembrane (MICA/B) and some GPI-anchored (ULBPs1-3) proteins. However, tumors grow in immunocompetent hosts due to complex tumor immune escape mechanisms that may compromise NKG2DL. Aim: we investigated early events produced during T lymphocyte-melanoma contact that may affect the quality of the tumoricidal response. We observed a cell-cell contact-dependent but NKG2D-NKG2DL interaction-independent increase in surface MICA on T lymphocytes upon a brief coculture with cell surface MICA+ melanomas. This phenomenon was due to transfer of MICA from the tumor cells to the T lymphocytes, being limited to NKG2DL with transmembrane domain. Sustained detection of MICA on the cell surface of the T cells was dependent of a continuous contact with tumor cells since this molecule was rapidly cleared from the cell surface by endocytosis when the tumor cells were separated from the T cells. Also, the transference of MICA was actively driven by the T lympchocytes but was independent of the tumor cell viability. Conclusion: T lymphocytes capture MICA from some tumors and introduce this molecule in the exogenous antigen processing pathway. These findings may constitute a novel mechanism of regulation of tumor immunity.