The virus-specific and allospecific cytotoxic T-lymphocyte response to lymphocytic choriomeningitis virus is modified in a subpopulation of CD8(+) T cells coexpressing the inhibitory major histocompatibility complex class I receptor Ly49G2.
The role of negatively signaling NK cell receptors of the Ly49 family on the specificity of the acute CD8(+) cytotoxic T-lymphocyte (CTL) response was investigated in lymphocytic choriomeningitis virus (LCMV)-infected C57BL/6 mice. Activated CD8(+) T cells coexpressing Ly49G2 expanded during LCMV infection, and T-cell receptor analyses by flow cytometry and CDR3 spectratyping revealed a unique polyclonal T-cell population in the Ly49G2(+) fraction. These cells lysed syngeneic targets infected with LCMV or coated with two of three LCMV immunodominant peptides examined. Transfection of these sensitive targets with H2D(d), a ligand for Ly49G2, inhibited lysis. This was reversed by antibody to Ly49G2, indicating effective negative signaling. LCMV characteristically induces an anti-H2(d) allospecific T-cell response that includes T-cell clones cross-reactive between allogeneic and LCMV-infected syngeneic targets. The CD8(+) Ly49G2(+) population mediated no allospecific killing, nor was any NK-like killing observed against YAC-1 cells. This study shows that CD8(+) Ly49G2(+) cells participate in the virus-induced CTL response but lyse a more restricted range of targets than the rest of the virus-induced CTL population.
Peacock
C D
CD
Department of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655, USA.
Lin
M Y
MY
Ortaldo
J R
JR
Welsh
R M
RM
D000818:Animals; D000950:Antigens, Ly; D002478:Cells, Cultured; D022801:Complementarity Determining Regions; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D055630:Receptors, NK Cell Lectin-Like; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D000950:Antigens, Ly; D022801:Complementarity Determining Regions; D006183:H-2 Antigens; D007135:Immunoglobulin Variable Region; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D055630:Receptors, NK Cell Lectin-Like