Persistent expression of CD94/NKG2 receptors by virus-specific CD8 T cells is initiated by TCR-mediated signals.
Subsets of CD8 T cells express receptors that are critical in regulating the activity of NK cells. To characterize the expression of these receptors on CD8 T cells we made use of transgenic mice that express a H-2Kb restricted TCR specific for the immunodominant epitope located within the HSV-1 glycoprotein B (gB). Few naive gB-specific T cells express Ly49 or CD94/NKG2 receptors. Following acute infection of C57BL/6 mice with either HSV-1 or a recombinant influenza virus that encodes the gB determinant, gB-specific T cells showed a dramatic upregulation of CD94/NKG2 receptors. Moreover, gB-specific CD8 T cells that expressed CD94/NKG2 receptors were also found to express another NK receptor, KLRG1. We established that while Ag-stimulated gB-specific CD8 T cells primarily express inhibitory isoforms of CD94/NKG2 receptors, these cells remain capable of producing gammaIFN upon peptide stimulation. While peak CD94/NKG2 expression on gB-specific cells was reached 2-3 days following infection, it remained elevated beyond 60 days post-infection with either HSV-1 or a gB-expressing recombinant influenza virus. The data imply that the prolonged expression was not due to persistence of replicating virus and suggest that while recognition of the cognate Ag is necessary to trigger expression of CD94/NKG2 receptors, it is not required for their continued expression on memory T cells.
Department of Microbiology and Immunology, University of Melbourne, Royal Parade, Parkville, 3052 Australia.
Magdalena
M
Wojtasiak
Claerwen M
CM
Jones
Lucy C
LC
Sullivan
Adam C
AC
Winterhalter
Francis R
FR
Carbone
Andrew G
AG
Brooks
D000818:Animals; D015703:Antigens, CD / Q000032:analysis* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D037181:Lectins, C-Type / Q000032:analysis* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D051920:NK Cell Lectin-Like Receptor Subfamily D; D009975:Orthomyxoviridae / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011971:Receptors, Immunologic / Q000032:analysis* / Q000502:physiology; D055607:Receptors, Natural Killer Cell; D014759:Viral Envelope Proteins / Q000276:immunology*
D015703:Antigens, CD; C497870:Klrd1 protein, mouse; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus