The Journal of Experimental Medicine
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Journal of Experimental Medicine, Vol 181, 493-502, Copyright © 1995 by Rockefeller University Press


ARTICLES

Cells expressing a major histocompatibility complex class I molecule with a single covalently bound peptide are highly immunogenic

E Mottez, P Langlade-Demoyen, H Gournier, F Martinon, J Maryanski, P Kourilsky and JP Abastado
Unite de Biologie Moleculaire du Gene, INSERM U277, Paris, France.

The major histocompatibility complex (MHC) class I molecules expressed at the cell surface are associated with a large number of different peptides so that the density of a given MHC-peptide complex is relatively low. Here we describe the properties of MHC class I molecules genetically attached to a single antigenic peptide. Cells expressing these fusion proteins are recognized by T cells specific for the particular MHC-peptide complex. Coculture of naive splenocytes with cells expressing these MHC-peptide fusion proteins and the B7.1 antigen allows the induction of primary cytotoxic T lymphocytes (CTL) in vitro. Injection of these cells into naive mice enhances the frequency of specific CTL precursors and protects against a subsequent challenge with a tumor or a virus bearing the antigenic peptide. Soluble MHC- peptide fusions were also produced in which all three components, that is, the heavy chain, beta 2-microglobulin and the peptide, have fused into a single-chain protein. The availability of MHC class I molecules bound to a single peptide provides valuable tools for the manipulation of CTL responses and the analysis of the selection processes in the thymus.
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