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.
Unité de Biologie Moléculaire du Gène, INSERM U277, Paris, France.
E
E
Mottez
P
P
Langlade-Demoyen
H
H
Gournier
F
F
Martinon
J
J
Maryanski
P
P
Kourilsky
J P
JP
Abastado
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