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

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American Society for Microbiology

RESUMO

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 H2Dd, a ligand for Ly49G2, inhibited lysis. This was reversed by antibody to Ly49G2, indicating effective negative signaling. LCMV characteristically induces an anti-H2d 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.

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