MINIMUM STRUCTURAL REQUIREMENTS FOR PEPTIDE PRESENTATION BY MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES - IMPLICATIONS IN INDUCTIONOF AUTOIMMUNITY

The precise mechanisms of failure of immunological tolerance to self p roteins are not known. Major histocompatibility complex (MHC) suscepti bility alleles, the target peptides, and T cells with anti-self reacti vity must be present to cause autoimmune diseases. Experimental autoim mune encephalomyelitis (EAE) is a murine model of a human autoimmune d isease, multiple sclerosis. In EAE, residues 1-11 of myelin basic prot ein (MBP) are the dominant disease-inducing determinants in PL/J and ( PL/J x SJL/J)F-1 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 anti gen presentation by MHC class II molecules. Many viral and bacterial p roteins;share short runs of amino acid similarity with host self prote ins, a phenomenon known as molecular mimicry. Since a six-residue pept ide can sensitize MBP-specific T cells to cause EAE, these results def ine a minimum sequence identity for molecular mimicry in autoimmunity.