Disease relevance of MR1

• To determine whether CD40L blockade resulted in long-term tolerance, mice protected by treatment with MR1 Ab were rechallenged for uveitis after circulating MR1 Ab levels dropped below the detection limit of ELISA [1].
• MR1 protected against death from radiation pneumonitis and fibrosis and dramatically reduced lung pathology as evidenced by a limited influx of inflammatory cells, minimal collagen deposition, and septal thickening [2].
• MR1 also prevented radiation-induced pulmonary mastocytosis and blunted expression of cyclooxygenase-2, a proinflammatory enzyme responsible for prostaglandin synthesis [2].
• These findings are used to interpret the observed orientation of the hemes in tetraheme redox proteins such as Flavocytochrome c(3) fumarate reductase (Ifc(3), PDB code 1QJD) of Shewanella frigidimarina, another flavocytochrome from the same bacterium (Fcc(3), 1E39) and a small tetraheme cytochrome of Shewanella oneidensis strain MR1 (1M1P) [3].
• Myofibrillogenesis regulator 1 gene (MR-1) mutation in an Omani family with paroxysmal nonkinesigenic dyskinesia [4].

High impact information on MR1

• Similarly, EAE was exacerbated in MR1-deficient mice, which lack V(alpha)19i T cells [5].
• T cells expressing an invariant V(alpha)19-J(alpha)33 T cell receptor alpha-chain (V(alpha)19i TCR) are restricted by the nonpolymorphic major histocompatibility complex class Ib molecule MR1 [5].
• MR1-treated mice developed severe EAU and strong cellular responses to interphotoreceptor retinoid binding protein, comparable to those of control mice [1].
• In this setting, long-term graft survival (>100 days) was achieved in MR1-treated mice, whereas control recipients rejected their grafts within 25 days [6].
• Injection of CD154 blocking monoclonal antibody (MR1) reduced the mononuclear infiltrate by 50% and had no effect on granulocyte recruitment 48 hours after inoculation of S. epidermidis [7].

Chemical compound and disease context of MR1

• The aim of this study was to describe the clinical features of a large Serbian family with paroxysmal nonkinesigenic dyskinesia (PNKD) and one of the two previously described mutations in the Myofibrillogenesis regulator 1 gene (MR-1), which causes an alanine-to-valine substitution at position 9 [8].

Biological context of MR1

• Sequence analysis identified a MR-1 missense mutation (c.20C>T; A7V) in the affected family members, whereas it was not present in five unaffected family members and 129 population controls [4].

Anatomical context of MR1

• In contrast, T-cell deficiency (in T-cell deficient [nu/nu] mice), disruption of the CD154 signaling (in knockout [KO] mice), or its blockade in WT recipients (after MR1 monoclonal antibody [mAb] treatment), virtually prevented hepatic I/R insult [9].
• C57BL/6 mice were pretreated with either nothing, MR1, or hamster IgG 24 h prior to a single dose of 15 Gray ionizing radiation to the thorax [2].

Other interactions of MR1

• In Groups 3, 4 and 6, MLR responses were not modified by the absence of CD40 or CD154 molecules, or MR1 and were similar to Group 1 [10].
• Here we report the beneficial effect of the chronic administration of a hamster anti-murine CD154 mAb, MR1, in prolonging islet graft survival in NOD mice [6].

Analytical, diagnostic and therapeutic context of MR1

• MR1 administration was effective in prolonging allograft survival, but did not provide permanent protection from diabetes recurrence [6].
• In this combination, a less dramatic yet substantial delay in diabetes recurrence was observed in the MR1-treated recipients when compared with the control group [6].
• Compared to Group 1, MR1 induced long-term survival of xenografts in Group 2, but not in Group 6, survival of islets was not prolonged significantly in Groups 3 and 4 [10].

References