Cells expressing a major histocompatibility complex class I molecule with a single covalently bound peptide are highly immunogenic.
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.
Mottez
E
E
Unité de Biologie Moléculaire du Gène, INSERM U277, Paris, France.
Langlade-Demoyen
P
P
Gournier
H
H
Martinon
F
F
Maryanski
J
J
Kourilsky
P
P
Abastado
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D002999:Clone Cells; D006224:Cricetinae; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D006825:Hybridomas; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D001613:beta 2-Microglobulin / Q000378:metabolism
D000954:Antigens, Surface; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D011993:Recombinant Fusion Proteins; D001613:beta 2-Microglobulin