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© The Rockefeller University Press, 0022-1007/1998/12/1993/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 11, December 7, 1998 1993-2005

Articles

Stability and Diversity of T Cell Receptor Repertoire Usage during Lymphocytic Choriomeningitis Virus Infection of Mice

Meei Yun Lin and Raymond M. Welsh

From the Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, Massachusetts 01655

Numerous studies have examined T cell receptor (TCR) usage of selected virus-specific T cell clones, yet little information is available regarding the stability and diversity of TCR repertoire usage during viral infections. Here, we analyzed the Vβ8.1 TCR repertoire directly ex vivo by complementarity-determining region 3 (CDR3) length spectratyping throughout the acute lymphocytic choriomeningitis virus (LCMV) infection, into memory, and under conditions of T cell clonal exhaustion. The Vβ8 population represented 30–35% of the LCMV-induced CD8+ T cells and included T cells recognizing several LCMV-encoded peptides, allowing for a comprehensive study of a multiclonal T cell response against a complex antigen. Genetically identical mice generated remarkably different T cell responses, as reflected by different spectratypes and different TCR sequences in same sized spectratype bands; however, a conserved CDR3 motif was found within some same sized bands. This indicated that meaningful studies on the evolution of the T cell repertoire required longitudinal studies within individual mice. Such longitudinal studies with peripheral blood lymphocyte samples showed that (a) the virus-induced T cell repertoire changes little during the apoptosis period after clearance of the viral antigens; (b) the LCMV infection dramatically skews the host T cell repertoire in the memory state; and (c) continuous selection of the T cell repertoire occurs under conditions of persistent infections.

Key Words: lymphocytic choriomeningitis virus • memory • T cell receptor • spectratype • mice

Address correspondence to Dr. Raymond Welsh, Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655. Phone: 508-856-5819; Fax: 508-856-5780; E-mail: RWelsh{at}bangate.ummed.edu

1 Abbreviations used in this paper: CDR3, complementarity-determining region 3; EXPT, experiment; GP, glycoprotein; LDA, limiting dilution assay; LCMV, lymphocytic choriomeningitis virus; NP, nucleoprotein; PB, peripheral blood; pCTL, precursor cytotoxic T lymphocyte; PEC, peritoneal exudate cell; pTh, precursor T helper cell; PV, Pichinde virus.


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