Detection of virus-specific T cells and CD8+ T-cell epitopes by acquisition of peptide-HLA-GFP complexes: analysis of T-cell phenotype and function in chronic viral infections.
Antigen-specific CD8+ T cells acquire peptide-major histocompatibility complex (MHC) clusters through T-cell receptor (TCR)-mediated endocytosis after specific antigen stimulation. We generated an antigen-presenting cell (APC) expressing human leukocyte antigen (HLA)-A*201 coupled to the enhanced green fluorescent protein (GFP), which delivered GFP to an antigen-specific T cell when pulsed with antigenic peptide. We quantitatively identified human T-cell lymphotropic virus type I (HTLV-I) Tax(11-19) peptide-specific T-cell populations in peripheral blood mononuclear cells (PBMCs) from patients with HTLV-I-associated neurologic disease and defined a new CD8+ T-cell epitope in the HTLV-I envelope region. Acquisition of peptide-HLA-GFP complexes by antigen-specific T cells could distinguish, with respect to phenotype and perforin production, T cells from the chronic viral infections cytomegalovirus and HTLV-I. This approach will be a powerful tool in understanding the role of antigen-specific T-cell responses in health and disease.
Tomaru
Utano
U
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Yamano
Yoshihisa
Y
Nagai
Masahiro
M
Maric
Dragan
D
Kaumaya
Previn T P
PT
Biddison
William
W
Jacobson
Steven
S
D000938:Antigen-Presenting Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000032:analysis; D002908:Chronic Disease; D003586:Cytomegalovirus Infections / Q000276:immunology; D049452:Green Fluorescent Proteins; D015234:HLA-A Antigens / Q000378:metabolism*; D006801:Humans; D016056:Immunodominant Epitopes; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000032:analysis; D015493:Paraparesis, Tropical Spastic / Q000276:immunology; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology*
D002352:Carrier Proteins; D015234:HLA-A Antigens; D016056:Immunodominant Epitopes; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D009363:Neoplasm Proteins; C120635:TAX1BP1 protein, human; D049452:Green Fluorescent Proteins