Presentation of a determinant by MHC class II can be prevented through competitive capture by a flanking determinant on a multideterminant peptide

• Published in: Journal of autoimmunity Vol. 31; no. 1; pp. 59 - 65
• Main Authors: Maverakis, Emanual, Beech, Jonathan T., Schneider, Susanne, Sercarz, Eli E.
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 01.08.2008; Elsevier
• Subjects: Allergy and Immunology; Animals; Antigen Presentation; Antigen processing; Autoantigens - immunology; Autoimmunity; Binding, Competitive - immunology; Biological and medical sciences; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - immunology; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Golli-MBP; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; Hybridomas; Lymphocyte Activation; MBP; Medical sciences; Mice; Multiple Sclerosis - immunology; Myelin Basic Protein; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - immunology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Self Tolerance - immunology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tolerance; Transcription Factors - chemistry; Transcription Factors - immunology; Autoimmunity; Tolerance; Golli-MBP; MBP; Antigen processing; Prevention; Immunopathology; Immunology; Peptides; Determinant; Class II histocompatibility antigen
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/j.jaut.2008.02.004

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.