The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/11/1319/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 9, November 1, 1999 1319-1328

Original Article

Selective Expansion of Cross-Reactive Cd8+ Memory T Cells by Viral Variants

John B.A.G. Haanena, Monika C. Wolkersa, Ada M. Kruisbeeka, and Ton N.M. Schumachera

a Department of Immunology, The Netherlands Cancer Institute, Amsterdam 1066 CX, The Netherlands
The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands.31-20-512-205731-20-512-2072

tschum{at}nki.nl

The role of memory T cells during the immune response against random antigenic variants has not been resolved. Here, we show by simultaneous staining with two tetrameric major histocompatibility complex (MHC)–peptide molecules, that the polyclonal CD8+ T cell response against a series of natural variants of the influenza A nucleoprotein epitope is completely dominated by infrequent cross-reactive T cells that expand from an original memory population. Based on both biochemical and functional criteria, these cross-reactive cytotoxic T cells productively recognize both the parental and the mutant epitope in vitro and in vivo. These results provide direct evidence that the repertoire of antigen-specific T cells used during an infection critically depends on prior antigen encounters, and indicate that polyclonal memory T cell populations can provide protection against a range of antigenic variants.

Key Words: influenza virus • major histocompatibility complex tetramers • peptides • C57BL mice • in vivo

1used in this paper: APC, allophycocyanin; HAU, hemagglutinin unit(s); NP, nucleoprotein; PI, propidium iodide

© 1999 The Rockefeller University Press


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