Minute quantities of a single immunodominant foreign epitope are presented as large nested sets by major histocompatibility complex class II molecules.
The processing and presentation of immunogenetic peptides is an obligate event in the generation of an immune response. However, the degree of complexity with which an immunogenic foreign epitope is presented is still unclear. This question was addressed by analyzing the naturally processed peptides generated from exogenously-derived hen egg white lysozyme (HEL) bound to the murine major histocompatibility complex (MHC) class II molecule, H-2Ak. Using reversed-phase chromatography (RPC), T cell hybridomas and mass spectrometry, 16 peptides were identified that contain the minimal MHC binding epitope 52-61. These peptides exhibited substantial N- and C-terminal extensions and ranged from 13-28 amino acids in length. In contrast, MHC class I molecules present peptides of 8-11 residues and each foreign epitope appears to be represented by only a single peptide. The data here also show that only approximately 0.8% of the total bound peptide was derived from this single HEL epitope. These findings provide direct evidence that relatively small amounts of processed peptide are required to stimulate an effective T cell response.
Vignali
D A
DA
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
Urban
R G
RG
Chicz
R M
RM
Strominger
J L
JL
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001324:Autoantigens / Q000378:metabolism; D000939:Epitopes; D006183:H-2 Antigens / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006825:Hybridomas; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D009113:Muramidase / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D000939:Epitopes; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D009113:Muramidase