Effects of vaccination with T cell receptor peptides: Epitope switching to a possible disease‐protective determinant of myelin basic protein that is cross‐reactive with a TCR BV peptide

Abstract

Summary Immunization of Lewis rats with guinea-pig myelin basic protein (Gp-MBP) induced T cell responses to primary and secondary encephalitogenic determinants, as well as to a third non-encephalitogenic epitope, residues 55±69. This sequence is of interest due to its protective activity against experimental autoimmune encephalomyelitis. Protection involved induction of MBP-55±69-speci®c T cells expressing cross-reactive TCR BV8S6 genes that activated regulatory T cells speci®c for TCR BV8S2 determinants expressed on encephalitogenic T cells. We here present and discuss new evidence suggesting a possible immunological crossreactivity between the protective Gp-MBP-55±69 peptide and the regulatory BV8S2-39±59 peptide. This crossreactivity, which may also occur between the human MBP-55±74 peptide and the BV12S2-38±58 sequence, has potentially important implications for human diseases such as multiple sclerosis.

Contribution of peptides to multiple sclerosis research

“…All of the hMBP peptides tested showed binding affinity for at least one of the DR molecules analyzed, but only the three peptides MBP (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32), MBP (84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103), and MBP(144-163) were found capable of binding to three or more DR molecules. The peptide hMBP (84)(85)(86)(87)(88)(89)(90)(91)(92)(93)…”

“…This cross-reactivity can also occur between the human peptide MBP(55-74) (DSHHPARTAHYGS-LPQK) and the BV12S2(38-58) (DLGHGLRLIHY-SYGVQD) sequence. 15 A large panel of DR2-and DR4-restricted TCCs specific for the MBP(83-99) peptide were examined for the recognition motifs and structural requirements by Ala scanning. Although the recognition motifs of the TCCs were diverse, the TCR contact residues within MBP(83-99) were highly conserved.…”

“…27 , inducing relapsing EAE in ABH (Ag7) mice, is associated with broadening of the autoimmune repertoire, providing a dynamic model to evaluate the efficacy of peptide analogues. To determine the key residues within MOG (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) and PLP (56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70) for EAE in ABH mice, the core residues were substituted with Lys or Ala. Subtle changes in MOG(8-21) (PGYPIRALVG-DEAE) dramatically influenced disease susceptibility and T-cell responses in vitro.…”