HLA class II transgenic mice as models of human diseases

Veena D Taneja, Chella S. David

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Predisposition to develop various autoimmune disorders has been associated with certain HLA class II molecules but there is a lack of information on the pathophysiological role of HLA genes in conferring susceptibility. Various experimental animal models of autoimmune disease have been studied to address the role of immune response genes. To study the interactions involved between class II molecules (DQ and DR) and define the immunologic mechanisms in various diseases, we generated HLA-DR and DQ transgenic mice that lacked endogenous class II molecules. The HLA molecules in these mice are expressed on the cell surface and can positively select CD4+ T cells expressing various Vβ T-cell receptors (TCR). A peripheral tolerance is maintained to transgenic HLA molecules thus indicating that these molecules act as self. Mouse co-stimulatory and accessory molecules can interact with the HLA-peptide-TCR complex leading to efficient T-cell activation. In this review we describe immunogenetic models for human diseases using these transgenic mice. Our studies show that HLA class II transgene-restricted T cells recognize the immunodominant antigens and peptide epitopes, similar to HLA class II-restricted human T cells. Thus these mice provide powerful tools to understand the role of HLA class II molecules in predisposition and onset of human diseases and to develop immunotherapy and vaccines.

Original languageEnglish (US)
Pages (from-to)67-79
Number of pages13
JournalImmunological Reviews
Volume169
DOIs
StatePublished - 1999

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Transgenic Mice
T-Lymphocytes
T-Cell Antigen Receptor
Peripheral Tolerance
HLA-DQ Antigens
Peptide T
Immunogenetics
Immunodominant Epitopes
HLA-DR Antigens
Transgenes
Immunotherapy
Genes
Autoimmune Diseases
Epitopes
Vaccines
Animal Models
Peptides

ASJC Scopus subject areas

  • Immunology

Cite this

HLA class II transgenic mice as models of human diseases. / Taneja, Veena D; David, Chella S.

In: Immunological Reviews, Vol. 169, 1999, p. 67-79.

Research output: Contribution to journalArticle

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