Specific lysis of targets expressing varicella-zoster virus gpI or gpIV by CD4+ human T-cell clones.
Varicella-zoster virus (VZV)-specific CD4-positive T cells are known to lyse targets expressing VZV antigen, but little is known of the glycoprotein specificity or phenotype of these cells. To test the ability of T cells to distinguish between gpI and gpIV (which share an antibody-defined epitope), we prepared clones from blood from four healthy individuals by limiting dilution. Among 68 T-cell clones from four donors which were VZV specific in tests of proliferation, 30 lysed autologous Epstein-Barr virus-transformed lymphoblasts which had been superinfected with a recombinant vaccinia virus which included the whole VZV gpI sequence. These clones were characterized as major histocompatibility complex class II restricted by inhibition of their cytotoxicity with HLA-DR and CD4 monoclonal antibodies. Twenty-one clones lysed targets expressing gpIV. Fifteen of these clones lysed targets expressing gpI and gpIV. Four clones with gpI-gpIV specificity were examined in detail, and their dual specificity was confirmed by cold target inhibition. These four clones failed to kill target cells infected with a mutant gpIV recombinant vaccinia virus from which amino acid residues 212 to 354 had been deleted. This region includes one of the two gpIV decapeptides which have 50% homology with amino acids 111 to 121 of gpI. Our data confirm that T-cell-receptor-associated structures are required for specific lysis of VZV targets and indicate that (i) gpI-specific CD4 cytotoxic T cells outnumber gpIV-specific T cells in blood and (ii) 50% of gpI-specific T-cell clones also lyse gpIV-expressing targets.
Huang
Z
Z
Department of Pediatrics, University of Colorado, Denver 80262.
Vafai
A
A
Lee
J
J
Mahalingam
R
R
Hayward
A R
AR
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002472:Cell Transformation, Viral; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D006566:Herpesviridae Infections / Q000276:immunology*; D014645:Herpesvirus 3, Human / Q000472:pathogenicity*; D004854:Herpesvirus 4, Human; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012680:Sensitivity and Specificity; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D014759:Viral Envelope Proteins; C056913:glycoprotein E, varicella-zoster virus; C070916:glycoprotein IV, varicella-zoster virus