Dominant TCR V alpha usage by virus and tumor-reactive T cells with wide affinity ranges for their specific antigens.
We have studied the TCR features and functional responses of three sets of human cytolytic T cell (CTL) clones, recognizing antigenic peptides presented by HLA-A2 and derived from the Epstein-Barr virus proteins BMLF1 and BRLF1 and from the melanoma protein Melan-A/MART-1. Within each set, a majority of clones used a recurrent V alpha region, even though they expressed highly diverse TCR beta chains and V(D)J junctional sequences. Functional assays and peptide/MHC multimer binding studies indicated that this restricted V alpha usage was not associated with the affinity/avidity of the CTL clones. The V alpha dominance, which may be a frequent feature of antigen-specific T cells, likely reflects a restricted geometry of TCR/peptide/MHC complexes, primarily determined by V alpha CDR.
Trautmann
Lydie
L
INSERM U463, Institut de Biologie, Nantes, France.
Labarrière
Nathalie
N
Jotereau
Francine
F
Karanikas
Vaios
V
Gervois
Nadine
N
Connerotte
Thierry
T
Coulie
Pierre
P
Bonneville
Marc
M
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm; D022801:Complementarity Determining Regions; D015789:HLA-A2 Antigen / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015534:Trans-Activators / Q000276:immunology; D014764:Viral Proteins
D000951:Antigens, Neoplasm; C068382:BRLF1 protein, Human herpesvirus 4; D022801:Complementarity Determining Regions; D015789:HLA-A2 Antigen; D017874:Immediate-Early Proteins; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C090236:SM protein, Human herpesvirus 4; D015534:Trans-Activators; D014764:Viral Proteins