DM determines the cryptic and immunodominant fate of T cell epitopes.
The ability of the immune system to focus T cell responses against a select number of potential epitopes of a complex antigen is termed immunodominance. Epitopes that trigger potent T cell activation, after in vivo priming, are classified as immunodominant. By contrast, determinants that fail to elicit any response are called cryptic. DM, a major histocompatibility complex (MHC) heterodimer, plays a pivotal role in the presentation of MHC class II-restricted epitopes by catalyzing the exchange of class II-associated invariant chain peptide with the antigen-derived peptides within the MHC class II binding groove. Using L cells transfected with genes for MHC class II, invariant chain, and DM, we have studied the contribution of DM in the presentation of two cryptic (peptide 11-25 and peptide 20-35) and one dominant (peptide 106-116) epitope of hen egg white lysozyme (HEL). Cells lacking DM heterodimers efficiently display the determinants HEL 11-25 and HEL 20-35 to T cells. Strikingly, however, cells expressing DM are severely compromised in their ability to present the cryptic HEL 11-25/A(d) and 20-35/A(d) epitopes. DM-mediated antagonism of HEL 11-25/A(d) and 20-35/A(d) presentation could thus be central to 11-25/A(d) and 20-35/A(d) being cryptic epitopes in the HEL system. Interestingly, the display of the immunodominant epitope of HEL, 106-116/E(d), and of a dominant epitope of sperm whale myoglobin (SWM), 102-118/A(d), is entirely dependent on the expression of DM. Thus, cells lacking DM molecules are unable to efficiently express HEL 106-116/E(d) and SWM 102-118/A(d) determinants. We conclude that the DM heterodimers direct the immunodominant and cryptic fate of antigenic epitopes in vivo.
Nanda
N K
NK
Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois 60612, USA. navreetn@uic.edu
Sant
A J
AJ
D000818:Animals; D019281:Dimerization; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D007111:Immunity, Cellular; D016056:Immunodominant Epitopes / Q000276:immunology*; D007739:L Cells; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D009113:Muramidase / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D011994:Recombinant Proteins; D009113:Muramidase