Presentation of a determinant by MHC class II can be prevented through competitive capture by a flanking determinant on a multideterminant peptide.
Competitive capture is a process by which different determinants of an unfolding antigen compete for binding to the same MHC class II molecule. The "winning" determinant is then dominantly displayed. For self antigens, T cells with specificity for dominantly displayed determinants will be subject to strong tolerance induction. With this in mind we set out to characterize the determinant hierarchy of the junctional region of the Golli-MBP complex. Within this region the MBP 1-9 determinant is known to be a strong inducer of experimental autoimmune encephalomyelitis. We found that the Golli-MBP junctional region contains a triad of three overlapping determinants: LDVM1-5, MBP 1-9, and MBP 7-20. We demonstrate that these three determinants are unique and compete for binding to I-A(u) and that a determinant hierarchy exists with MBP 7-20 being the most dominantly displayed determinant. Because of the prevention of MBP1-9 access to MHC-II, the residual T cell repertoire to this determinant remains complete, thereby permitting its highest affinity members to drive the response, and to convert MBP1-9 into a dominant determinant, despite its poor MHC binding capacity.
Maverakis
Emanual
E
Division of Immune Regulation, Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA. emaverakis@yahoo.com
Beech
Jonathan T
JT
Schneider
Susanne
S
Sercarz
Eli E
EE
D000818:Animals; D017951:Antigen Presentation; D001324:Autoantigens / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006825:Hybridomas; D008213:Lymphocyte Activation; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000276:immunology
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C499047:Mbp protein, mouse; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D014157:Transcription Factors