Minimum structural requirements for peptide presentation by major histocompatibility complex class II molecules: implications in induction of autoimmunity
| Autor: | Hugh O. McDevitt, Dawn E. Smilek, Lawrence Steinman, Christopher Lock, C.I. Pearson, Anand M. Gautam |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Encephalomyelitis
Autoimmune Experimental T-Lymphocytes Antigen presentation Molecular Sequence Data Autoimmunity Major histocompatibility complex medicine.disease_cause Lymphocyte Activation Immune tolerance Mice Structure-Activity Relationship medicine Immune Tolerance Animals Amino Acid Sequence Peptide sequence MHC class II Antigen Presentation Multidisciplinary biology Experimental autoimmune encephalomyelitis Histocompatibility Antigens Class II Myelin Basic Protein medicine.disease Myelin basic protein Molecular mimicry Immunology biology.protein Oligopeptides Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 91(2) |
| ISSN: | 0027-8424 |
| Popis: | The precise mechanisms of failure of immunological tolerance to self proteins are not known. Major histocompatibility complex (MHC) susceptibility alleles, the target peptides, and T cells with anti-self reactivity must be present to cause autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE) is a murine model of a human autoimmune disease, multiple sclerosis. In EAE, residues 1-11 of myelin basic protein (MBP) are the dominant disease-inducing determinants in PL/J and (PL/J x SJL/J)F1 mice. Here we report that a six-residue peptide (five of them native) of MBP can induce EAE. Using peptide analogues of the MBP-(1-11) peptide, we demonstrate that only four native MBP residues are required to stimulate MBP-specific T cells. Therefore, this study demonstrates lower minimum structural requirements for effective antigen presentation by MHC class II molecules. Many viral and bacterial proteins share short runs of amino acid similarity with host self proteins, a phenomenon known as molecular mimicry. Since a six-residue peptide can sensitize MBP-specific T cells to cause EAE, these results define a minimum sequence identity for molecular mimicry in autoimmunity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|