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Journal of Virology, August 2000, p. 7032-7038, Vol. 74, No. 15
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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

Craig D. Peacock,1 Meei Y. Lin,1 John R. Ortaldo,2 and Raymond M. Welsh1,*

Department of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655,1 and Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 217022

Received 10 February 2000/Accepted 4 May 2000

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.

* Corresponding author. Mailing address: Department of Pathology, University of Massachusetts Medical Center, 55 Lake Ave. North, Worcester, MA 01655. Phone: (508) 856-5819. Fax: (508) 856-5780. E-mail: Raymond.Welsh{at}umassmed.edu.

Journal of Virology, August 2000, p. 7032-7038, Vol. 74, No. 15
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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