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J Virol, May 1998, p. 3999-4004, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Predominance of HLA-Restricted Cytotoxic T-Lymphocyte Responses to Serotype-Cross-Reactive Epitopes on Nonstructural Proteins following Natural Secondary Dengue Virus Infection

Anuja Mathew,1 Ichiro Kurane,1,dagger Sharone Green,1 Henry A. F. Stephens,2 David W. Vaughn,3 Siripen Kalayanarooj,4 Saroj Suntayakorn,5 Dasnayanee Chandanayingyong,6 Francis A. Ennis,1 and Alan L. Rothman1,*

Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical Center, Worcester, Massachusetts1; Division of Nephrology, The Middlesex Hospital, London, United Kingdom2; and Department of Virology, Armed Forces Research Institute of Medical Sciences,3 Queen Sirikit National Institute for Child Health (formerly Bangkok Children's Hospital),4 and Department of Transfusion Medicine, Siriraj Hospital,6 Bangkok, and Kamphaeng Phet Provincial Hospital, Kamphaeng Phet,5 Thailand

Received 23 December 1997/Accepted 9 February 1998

We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after natural symptomatic secondary dengue virus infection. In all four patients analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue virus proteins. Numerous CD4+ and CD8+ CTL lines were generated from the bulk cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived from both patients were cross-reactive with other serotypes of dengue virus. The CD8+ NS1.2a-specific lines from patient KPP94-037 were HLA B57 restricted, and the CD8+ NS3-specific lines from patient KPP94-024 were HLA B7 restricted. The CD4+ CTL lines from patient KPP94-037 were HLA DR7 restricted. A majority of the CD8+ CTLs isolated from patient KPP94-024 were found to recognize amino acids 221 to 232 on NS3. These results demonstrate that in Thai patients after symptomatic secondary natural dengue infections, CTLs are mainly directed against nonstructural proteins and are broadly cross-reactive.

* Corresponding author. Mailing address: Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical Center, 55 Lake Ave. North, Worcester, MA 01655. Phone: (508) 856-4182. Fax: (508) 856-4890. E-mail: Alan.Rothman{at}ummed.edu.

dagger Present address: Department of Microbiology, Kinki University School of Medicine, Osaka, Japan.

J Virol, May 1998, p. 3999-4004, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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