Suscripción a Biblioteca: Guest
Portal Digitalde Biblioteca Digital eLibros Revistas Referencias y Libros de Ponencias Colecciones
Critical Reviews™ in Immunology
Factor de Impacto: 1.352 Factor de Impacto de 5 años: 3.347 SJR: 0.657 SNIP: 0.55 CiteScore™: 2.19

ISSN Imprimir: 1040-8401
ISSN En Línea: 2162-6472

Volumes:
Volumen 39, 2019 Volumen 38, 2018 Volumen 37, 2017 Volumen 36, 2016 Volumen 35, 2015 Volumen 34, 2014 Volumen 33, 2013 Volumen 32, 2012 Volumen 31, 2011 Volumen 30, 2010 Volumen 29, 2009 Volumen 28, 2008 Volumen 27, 2007 Volumen 26, 2006 Volumen 25, 2005 Volumen 24, 2004 Volumen 23, 2003 Volumen 22, 2002 Volumen 21, 2001 Volumen 20, 2000 Volumen 19, 1999 Volumen 18, 1998 Volumen 17, 1997 Volumen 16, 1996 Volumen 15, 1995 Volumen 14, 1994

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v27.i3.60
pages 271-288

Targeting the Antigen-Binding Site of HLA-Restricting Alleles in Treatment of Autoimmune Disease

Minako Oshima
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Philip Deitiker
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas
M. Zouhair Atassi
Baylor College of Medicine Houston, TX 77030

SINOPSIS

In autoimmune disease, production of disease-causing auto-antibodies (Abs) depends on autoreactive T cells that recognize the epitopes of the pathogenic antigen in the context of MHC class II molecules. It is possible that selective inhibition of an antigen-presenting function of disease-associated MHC alleles could lead to suppression of the disease. Myasthenia gravis (MG) is a disabling neuromuscular disease in which autoimmune responses against acetylcholine receptor (AChR), especially against the α chain of AChR, cause a postsynaptic defect. HLA linkage of MG has been thus far best detailed for DQB1. Recently, we have shown that certain DQ haplotypes are associated with presentation of AChR α-chain peptides in MG. In a mouse model for MG, which can be induced in disease-susceptible C57BL/6 (B6, H-2b) mice by injection with Torpedo AChR, region 62-76 of I-Ab β chain is involved in the disease mechanism. Monoclonal Abs (mAbs) against synthetic peptide I-Aβb62-76, which localizes at the rim of the antigen-binding site of I-Ab, inhibited in vitro proliferation of disease-associated T cells. Passive transfer of these mAbs as well as vaccination with this peptide strongly suppressed occurrence of clinical MG in B6 mice. In both cases, Ab and T-cell responses against AChR, especially those related to disease pathogenesis, also decreased. mAbs against peptides from the ridge of the antigen-binding region of the correlate DQB1 sequences inhibited in vitro the proliferation of AChR-specific T cells from MG patients. The results indicated that the function of disease-associated MHC alleles may be blocked by directly and selectively targeting the antigen-presenting region on these MHC molecules. The strategy could provide an effective means for immunointervention in other autoimmune and allergic responses.


Articles with similar content:

On the Initial Trigger of Myasthenia Gravis and Suppression of the Disease by Antibodies Against the MHC Peptide Region Involved in the Presentation of a Pathogenic T-Cell Epitope
Critical Reviews™ in Immunology, Vol.21, 2001, issue 1-3
Philip Deitiker, Minako Oshima, M. Zouhair Atassi
Neuronal Derivative Mediators That Regulate Cutaneous Inflammations
Critical Reviews™ in Immunology, Vol.32, 2012, issue 4
So-ichiro Fukada, Norihisa Mikami, Hiroshi Yamamoto, Kazutake Tsujikawa
Autoimmunity and the Immunotherapy of Cancer: Targeting the "Self" to Destroy the "Other"
Critical Reviews™ in Immunology, Vol.20, 2000, issue 6
Nicholas P. Restifo, Willem W. Overwijk
Opportunities for Translation from the Bench: Therapeutic Intervention of the JAK/STAT Pathway in Neuroinflammatory Diseases
Critical Reviews™ in Immunology, Vol.35, 2015, issue 6
Yudong Liu, Etty N. Benveniste, Hongwei Qin, Sara A. Gibson
T-Cell Control of Immunity to the Asexual Blood Stages of the Malaria Parasite
Critical Reviews™ in Immunology, Vol.14, 1994, issue 2
Klavs Berzins, Marita Troye-Blomberg, Peter Perlmann