The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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© The Rockefeller University Press, 0022-1007/1997/6/2043/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 12, June 16, 1997 2043-2051


Articles

HLA-A2.1–restricted Education and Cytolytic Activity of CD8+ T Lymphocytes from β2 Microglobulin (β2m) HLA-A2.1 Monochain Transgenic H-2Db β2m Double Knockout Mice

Steve Pascolo*, Nathalie Bervas*, Jan M. Ure{ddagger}, Austin G. Smith{ddagger}, François A. Lemonnier*, and Béatrice Pérarnau*

From the * Institut Pasteur, Département SIDA-Rétrovirus, Unité d'Immunité Cellulaire Antivirale, 75724 Paris Cedex 15, France; and {ddagger} Gene Targeting Laboratory, Centre for Genome Research, University of Edinburgh, Edinburgh EH9 3JQ, United Kingdom

Three different HLA-A2.1 monochains were engineered in which either the human or mouse β2-microglobulin (β2m) is covalently linked to the NH2 terminus of the heavy chain by a 15– amino acid long peptide: HHH, entirely human, HHD, with the mouse H-2Db {alpha}3, transmembrane, and cytoplasmic domains, and MHD, homologous to HHD but linked to the mouse β2mb. The cell surface expression and immunological capacities of the three monochains were compared with transfected cells, and the selected HHD construct was introduced by transgenesis in H-2Db–/– β2m–/– double knockout mice. Expression of this monochain restores a sizable peripheral CD8+ T cell repertoire essentially educated on the transgenic human molecule. Consequently, infected HHD, H-2Db–/– β2m–/– mice generate only HLA-A2.1–restricted CD8+ CTL responses against influenza A and vaccinia viruses. Interestingly, the CTL response to influenza A virus is mostly, if not exclusively, directed to the 58-66 matrix peptide which is the HLA-A2.1–restricted immunodominant epitope in humans. Such mice might constitute a versatile animal model for the study of HLA-A2.1–restricted CTL responses of vaccine interest.


Address correspondence to Béatrice Pérarnau, Institut Pasteur, Département SIDA-Rétrovirus, Unité d'Immunité Cellulaire Antivirale, 28 rue du Dr Roux, 75724 Paris Cedex 15, France. The present address of S. Pascolo is IMBB, Forth-Hellas P.O. Box 1527, Vassilika Vouton, Heraklion 711 10, Crete, Greece.

During her postdoctoral stay at the Centre for Genome Research (Edinburgh, U.K.), B. Pérarnau was a recipient of a fellowship from the Human Frontier Science Program Organisation. The Centre for Genome Research is supported by the Biotechnology and Biological Sciences Research Council of the United Kingdom. This work was funded by the Institut Pasteur and by grants from the Association pour la Recherche contre le Cancer, the Ligue contre le Cancer, and the Pasteur-Weizmann committees.

1Abbreviations used in this paper: β2m, β-2 microglobulin; HA, hemagglutinin; TAP, transporter associated with antigen presentation.


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