Molecular anatomy of antigen-specific CD8(+) T cell engagement and synapse formation in vivo.
Antigen-specific CD8(+) T cells are required for the clearance of most viral infections and several cancers. However, it is not clear in vivo whether CD8(+) T cells can engage multiple targets simultaneously, engagement results in the formation of an immunologic synapse or molecules involved in CD8 function are redistributed to the synapse. We used here high-resolution microscopy to visualize interactions between virus-specific effectors and target cells in vivo. Using either in situ tetramer staining or green fluorescent protein-labeled virus-specific T cells, we have shown that a single CD8(+) T cell can engage two or three targets, a synapse occurs at the site of engagement and molecules involved in attachment (lymphocyte function-associated antigen 1), signaling (Lck) and lytic activity (perforin) are differentially positioned on the T cell. In addition, we have established an in vivo approach for assessing the intricacies of antigen-specific T cell activation, migration, engagement, memory and other defining elements of adaptive immunity.
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001921:Brain / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009698:Nucleoproteins / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013194:Staining and Labeling; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D052899:Pore Forming Cytotoxic Proteins; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus; C094246:nucleoprotein peptide 118-126, lymphocytic choriomeningitis virus; D054353:Perforin; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)