For COVID-19 vaccine updates, please review our information guide. For patient eligibility and scheduling availability, please visit VaccineTogetherNY.org.

Competition between two MHC binding registers in a single peptide processed from myelin basic protein influences tolerance and susceptibility to autoimmunity.

TitleCompetition between two MHC binding registers in a single peptide processed from myelin basic protein influences tolerance and susceptibility to autoimmunity.
Publication TypeJournal Article
Year of Publication2003
AuthorsSeamons A, Sutton J, Bai D, Baird E, Bonn N, Kafsack BFC, Shabanowitz J, Hunt DF, Beeson C, Goverman J
JournalJ Exp Med
Volume197
Issue10
Pagination1391-7
Date Published2003 May 19
ISSN0022-1007
KeywordsAnimals, Antigen Presentation, Autoimmunity, Binding, Competitive, Epitopes, Histocompatibility Antigens Class II, Immune Tolerance, Mice, Myelin Basic Protein, Peptide Fragments, T-Lymphocytes
Abstract

Experimental allergic encephalomyelitis (EAE) is an animal model for multiple sclerosis induced by stimulating myelin basic protein (MBP)-specific T cells. The MBP-specific repertoire in B10.PL mice is shaped by tolerance mechanisms that eliminate MBP121-150-specific T cells. In contrast, MBPAc1-11-specific T cells escape tolerance and constitute the encephalitogenic repertoire. To determine if this differential tolerance is caused by differences in the abundance of MBP epitopes generated by processing, MBP peptides were eluted from I-Au complexes and analyzed by mass spectrometry. Peptides were identified from both the NH2-terminal and MBP121-150 regions. Unexpectedly, MBPAc1-18 and Ac1-17, which contain the MBPAc1-11 epitope, were much more abundant than MBP121-150 peptides. The results demonstrate that competition between two I-Au binding registers, a low affinity register defined by MBPAc1-11 and a high affinity register defined by MBP5-16, prevents most of the NH2-terminal naturally processed peptides from binding in the MBPAc1-11 register. The small fraction of MBPAc1-18 bound in the MBPAc1-11 register is not sufficient to induce tolerance but provides a ligand for MBPAc1-11-specific T cells during disease. These results provide a basis for both the lack of tolerance to MBPAc1-11 and the ability of this epitope to become a target during autoimmunity.

DOI10.1084/jem.20022226
Alternate JournalJ Exp Med
PubMed ID12756272
PubMed Central IDPMC2193784
Grant ListR01-NS35126 / NS / NINDS NIH HHS / United States
R01 AI33993 / AI / NIAID NIH HHS / United States
T32 HG000035 / HG / NHGRI NIH HHS / United States
R01 NS035126 / NS / NINDS NIH HHS / United States
R37 AI033993 / AI / NIAID NIH HHS / United States
T32 HG00035 / HG / NHGRI NIH HHS / United States
R01 AI033993 / AI / NIAID NIH HHS / United States

Weill Cornell Medicine Microbiology and Immunology 1300 York Avenue, Box 62 New York, NY 10065 Phone: (212) 746-6505 Fax: (212) 746-8587