Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

MHC structure and autoimmune T cell repertoire development.

W M Ridgway1, C G Fathman

  • 1University of Pittsburgh School of Medicine, Department of Medicine, PA 15261, USA. ridgway2@pitt.edu

Current Opinion in Immunology
|January 13, 2000
PubMed
Summary

This study clarifies how Major Histocompatibility Complex (MHC) structure influences T cell development and autoimmune disease risk. Defective thymic selection, particularly involving MHC class II I-Ag7, underlies susceptibility to autoimmune diabetes.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Endogenous interleukin-22 protects against inflammatory bowel disease but not autoimmune cholangitis in dominant negative form of transforming growth factor beta receptor type II mice.

Clinical and experimental immunology·2016
Same author

Successful immunotherapy of autoimmune cholangitis by adoptive transfer of forkhead box protein 3(+) regulatory T cells.

Clinical and experimental immunology·2014
Same author

Escherichia coli infection induces autoimmune cholangitis and anti-mitochondrial antibodies in non-obese diabetic (NOD).B6 (Idd10/Idd18) mice.

Clinical and experimental immunology·2013
Same author

Dengue-2 structural proteins associate with human proteins to produce a coagulation and innate immune response biased interactome.

BMC infectious diseases·2011
Same author

Induction of autoimmune cholangitis in non-obese diabetic (NOD).1101 mice following a chemical xenobiotic immunization.

Clinical and experimental immunology·2008
Same author

Preservation of self: an overview of E3 ubiquitin ligases and T cell tolerance.

Seminars in immunology·2007

Area of Science:

  • Immunology
  • Genetics
  • Molecular Biology

Background:

  • The development of the peripheral T cell repertoire is crucial for immune system function and preventing autoimmunity.
  • Major Histocompatibility Complex (MHC) molecules play a central role in T cell selection within the thymus.
  • Alterations in MHC structure are implicated in the pathogenesis of autoimmune diseases.

Purpose of the Study:

  • To elucidate the relationship between MHC structure and thymic selection processes.
  • To investigate the role of the unique MHC class II molecule I-Ag7 in the nonobese diabetic mouse model of autoimmune diabetes.
  • To compare findings in murine models with human MHC alleles associated with autoimmune disease susceptibility and resistance.

Main Methods:

  • Biochemical analysis of the I-Ag7 MHC class II molecule.

Related Experiment Videos

  • Analysis of T cell repertoire selection influenced by I-Ag7.
  • Structural analysis of human MHC alleles (DQA1*0301 DQB1*0302 and DQA1*0102 DQB1*0602).
  • Comparative studies using transgenic and knockout models of autoimmune diseases.

    • Main Results:

    • Biochemical and repertoire selection data support a model where defective thymic selection, driven by specific MHC molecules like I-Ag7, contributes to autoimmune disease.
    • Structural and functional analyses of human MHC alleles reveal their impact on autoimmune repertoire selection.
    • Integrated findings from spontaneous and experimental models highlight the significance of T cell avidity in thymic selection and autoimmunity predisposition.

    Conclusions:

    • Defective thymic selection due to specific MHC structures is a key mechanism underlying autoimmune disease susceptibility.
    • Understanding MHC-driven repertoire selection provides insights into the genetic predisposition to autoimmune conditions like diabetes.
    • Avidity considerations during thymic selection are critical factors influencing an individual's risk of developing autoimmunity.