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Department of Biochemistry and Molecular Biology

Houston, Texas

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Verna and Marrs McLean Department of Biochemistry and Molecular Biology
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Minako Oshima, Ph.D.

Assistant Professor
Department of Biochemistry and Molecular Biology

moshima@bcm.edu

Education

  • Ph.D., Kurume University School of Medicine
  • Postdoctoral, Kurume University School of Medicine
  • Postdoctoral, Baylor College of Medicine

Immuno-suppression of autoimmune disease / Disease mechanisms involving auto-reactive T cells in autoimmunity

Research area includes: 1) immuno-suppression of autoimmune disease by targeting MHC, 2) investigation of the role of auto-reactive T cells in the pathogenesis of autoimmune disease, 3) determination of MHC class II-restricted pathogenic epitope regions of autoantigen in autoimmune disease, and 4) development of improved induction methods for experimental autoimmune disease.

Autoimmune diseases result from immune responses of a host immune system to self antigens (Ags). Production of disease-causing auto-antibodies (Abs) in most autoimmune diseases depends on auto-reactive T cells that recognize the epitopes of the pathogenic Ags in the context of MHC class II molecules.

  1. There has been growing evidence showing that certain HLA alleles are associated with autoimmune disease. Inhibition of the Ag-presenting function of disease-related MHC class II alleles could lead to a regression of the auto-reactive T cell population. To prove this hypothesis, we used as a disease model myasthenia gravis (MG), in which acetylcholine receptor (AChR) is its major autoAg. We prepared mAbs against Ag-binding region of mouse MHC and various HLA DQ alleles that are disease-associated. We then tested their efficacy in vivo using a mouse model of MG, and in vitro using live AChR-specific T cells from patients with MG. Interim findings have been published.
  2. In MG, collaboration between T- and B-cells that recognize distinctive disease-associated regions of AChR ß-chain is responsible for the production of disease-causing Abs. We have identified T-cell epitope regions recognized by peripheral blood lymphocytes from a set of MG patients, and analyzed their responses in the presentation by HLA DQ allele types. Interim findings have been published. B-cell epitope regions that may have specific association with particular HLA alleles are currently under investigation by using samples from the same set of patients.
  3. Investigation on disease mechanism and/or treatment strategy of MG depends on the animal study using an animal (mouse) model of MG, termed experimental autoimmune MG (EAMG). There is a need to improve current protocol for induction of disease in a disease-susceptible mouse strain. Development of an efficient protocol for induction of mouse EAMG by using additional adjuvant is under investigation.
  4. Use of steroids in MG patients causes a decrease in their bone mass. However, B6 mice with induced clinical MG sometimes show weight loss, which might correlate with low bone mass. This might suggest that different process for reduction in bone mineral density might exist in the disease mechanism of MG. The study is underway with collaboration from bone research specialists in other institution.

Selected Publications

  • Deitiker PR, Oshima M, Jankovic J, Duane DD, Aoki KR, Atassi MZ. Association of HLA Class II alleles and haplotypes with cervical dystonia: HLA DR13-DQ6 (DQB1*0604) homozygotes are at greatly increased risk of cervical dystonia in Caucasian Americans. Autoimmunity. 2011 May;44(3):167-76. [PubMed]
  • Deitiker PR, Oshima M, Smith RG, Mosier D, Atassi MZ. Association with HLA DQ of early onset myasthenia gravis in Southeast Texas region of the United States. Int J Immunogenet. 2011 Feb;38(1):55-62. [PubMed]
  • Oshima M, Deitiker P, Atassi MZ. Targeting the antigen-binding site of HLA-restricting alleles in treatment of autoimmune disease. Crit Rev Immunol. 2007;27(3):271-88. [PubMed]
  • Deitiker PR, Oshima M, Smith RG, Mosier DR, Atassi MZ.Subtle differences in HLA DQ haplotype-associated presentation of AChR alpha-chain peptides may suffice to mediate myasthenia gravis. Autoimmunity. 2006 Jun;39(4):277-88. [PubMed]
  • Jha S, Xu K, Maruta T, Oshima M, Mosier DR, Atassi MZ, Hoch W. Myasthenia gravis induced in mice by immunization with the recombinant extracellular domain of rat muscle-specific kinase (MuSK). J Neuroimmunol. 2006 Jun;175(1-2):107-17. [PubMed]
  • Maruta T, Oshima M, Deitiker PR, Ohtani M, Atassi MZ. Use of alum and inactive Bordetella pertussis for generation of antibodies against synthetic peptides in mice. Immunol Invest. 2006;35(2):137-48. [PubMed]
  • Oshima M, Maruta T, Ohtani M, Deitiker PR, Mosier D, Atassi MZ. Vaccination with a MHC class II peptide in Alum and inactive pertussis strongly ameliorates clinical MG in C57BL/6 mice. J Neuroimmunol. 2006 Feb;171(1-2):8-16. [PubMed]
  • Oshima M, Deitiker PR, Mosier DR, Smith RG, Atassi MZ. Responses in vitro of peripheral blood lymphocytes from patients with myasthenia gravis to stimulation with human acetylcholine receptor alpha-chain peptides: analysis in relation to age, thymic abnormality, and ethnicity. Hum Immunol. 2005 Jan;66(1):32-42. [PubMed]
  • Oshima M, Ohtani M, Deitiker PR, Smith RG, Mosier DR, Atassi MZ. Suppression by mAbs against DQB1 peptides of in vitro proliferation of AChR-specific T cells from myasthenia gravis patients. Autoimmunity. 2005 Mar;38(2):161-9. [PubMed]
  • Oshima M, Deitiker P, Ashizawa T, Atassi MZ. Vaccination with a MHC class II peptide attenuates cellular and humoral responses against tAChR and suppresses clinical EAMG. Autoimmunity. 2002 May;35(3):183-90. [PubMed]
  • View more publications by Dr. Oshima.

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