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Journal of Virology, September 1999, p. 7619-7626, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The Cytotoxic T-Cell Response to Herpes Simplex Virus Type 1 Infection of C57BL/6 Mice Is Almost Entirely Directed against a Single Immunodominant Determinant

Morgan E. Wallace,1 Rachael Keating,1 William R. Heath,2 and Francis R. Carbone1,*

Department of Pathology and Immunology, Monash Medical School, Prahran, Victoria 3181,1 and Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050,2 Australia

Received 9 April 1999/Accepted 10 June 1999

Many virus infections give rise to surprisingly limited T-cell responses directed to very few immunodominant determinants. We have been examining the cytotoxic T-lymphocyte (CTL) response to herpes simplex virus type 1 (HSV-1) infection. Previous studies have identified the glycoprotein B-derived peptide from residues 498 to 505 (gB498-505) as one of at least three determinants recognized by HSV-1-specific CTLs isolated from C57BL/6 mice. We had previously found that in vitro-derived CTLs directed to gB498-505 show a characteristic pattern of T-cell receptor (TCR) usage, with 60% of gB498-505-specific CD8+ T cells expressing BV10+ TCR beta  chains and a further 20% expressing BV8S1. In this report, we confirm that this TCR V-region bias is also reflected in the ex vivo response to HSV-1 infection. A high proportion of activated CD8+ draining lymph node cells were found to express these dominant V regions, suggesting that a substantial number of in vivo responding T cells were directed to this one viral determinant. The use of an HSV-1 deletion mutant lacking the gB498-505 determinant in combination with accurate intracellular gamma interferon staining allowed us to quantify the extent of gB-specific T-cell dominance. Together, these results suggested that between 70 and 90% of all CD8+ HSV-1-specific T cells target gB498-505. While deletion of this determinant resulted in an attenuated CD8+ T-cell response, it also permitted the emergence of one or more previously unidentified cryptic specificities. Overall, HSV-1 infection of C57BL/6 mice results in an extremely focused pattern of CD8+ T-cell selection in terms of target specificity and TCR expression.

* Corresponding author. Mailing address: Department of Pathology and Immunology, Monash Medical School, Prahran, Victoria 3181, Australia. Phone: 61-3-9903-0744. Fax: 61-3-9903-0731. E-mail: carbone{at}cobra.path.monash.edu.au.

Journal of Virology, September 1999, p. 7619-7626, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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