The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/7/71/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 1, July 1, 1998 71-82

Articles

Conserved T Cell Receptor Repertoire in Primary and Memory CD8 T Cell Responses to an Acute Viral Infection

David J.D. Sourdive*,{ddagger},§, Kaja Murali-Krishna*,{ddagger}, John D. Altman*,{ddagger}, Allan J. Zajac*,{ddagger}, Jason K. Whitmire*,{ddagger}, Christophe Pannetier§,||, Philippe Kourilsky||, Brian Evavold{ddagger}, Alessandro Sette, and Rafi Ahmed*,{ddagger}

From the * Emory Vaccine Center, Rollins Research Center, and the {ddagger} Department of Microbiology and Immunology, Emory University, Atlanta, Georgia 30322; the § Centre d'Etudes du Bouchet, 91710 Vert-le-Petit, France; the || Unité de Biologie Moléculaire du Gène, Institut Pasteur, 75724 Paris cedex 15, France; and Epimmune, San Diego, California 92121

Viral infections often induce potent CD8 T cell responses that play a key role in antiviral immunity. After viral clearance, the vast majority of the expanded CD8 T cells undergo apoptosis, leaving behind a stable number of memory cells. The relationship between the CD8 T cells that clear the acute viral infection and the long-lived CD8 memory pool remaining in the individual is not fully understood. To address this issue, we examined the T cell receptor (TCR) repertoire of virus-specific CD8 T cells in the mouse model of infection with lymphocytic choriomeningitis virus (LCMV) using three approaches: (a) in vivo quantitative TCR β chain V segment and complementarity determining region 3 (CDR3) length repertoire analysis by spectratyping (immunoscope); (b) identification of LCMV-specific CD8 T cells with MHC class I tetramers containing viral peptide and costaining with TCR Vβ–specific antibodies; and (c) functional TCR fingerprinting based on recognition of variant peptides. We compared the repertoire of CD8 T cells responding to acute primary and secondary LCMV infections, together with that of virus-specific memory T cells in immune mice. Our analysis showed that CD8 T cells from several Vβ families participated in the anti-LCMV response directed to the dominant cytotoxic T lymphocyte (CTL) epitope (NP118–126). However, the bulk (~70%) of this CTL response was due to three privileged T cell populations systematically expanding during LCMV infection. Approximately 30% of the response consisted of Vβ10+ CD8 T cells with a β chain CDR3 length of nine amino acids, and 40% consisted of Vβ8.1+ (β CDR3 = eight amino acids) and Vβ8.2+ cells (β CDR3 = six amino acids). Finally, we showed that the TCR repertoire of the primary antiviral CD8 T cell response was similar both structurally and functionally to that of the memory pool and the secondary CD8 T cell effectors. These results suggest a stochastic selection of memory cells from the pool of CD8 T cells activated during primary infection.

Key Words: immunological memory • CD8 T cells • viral immunity • T cell receptor • lymphocytic choriomeningitis virus

Address correspondence to Rafi Ahmed, Emory Vaccine Center, Rollins Research Center, Emory University, Atlanta, GA 30322. Phone: 404-727-3571; Fax: 404-727-3722; E-mail: ra{at}microbio.emory.edu

C. Pannetier's current address is Laboratory of Immunology, National Institute of Allergies and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.

Abbreviations used: C, constant; D, diversity; ELISPOT, enzyme-linked immunospot; J, joining; LCMV, lymphocytic choriomeningitis virus; LDA, limiting dilution assay; PCC, pigeon cytochrome C; V, variable.


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