Identification of autoantigen epitopes in MHC class II transgenic mice

Immunol Rev. 1998 Aug;164:129-38. doi: 10.1111/j.1600-065x.1998.tb01215.x.

Abstract

MHC class II molecules function by selective binding of antigenic peptides, thereby both shaping the T-cell receptor (TCR) repertoire in the thymus and influencing presentation of immunogenic peptides to CD4+ T cells in the periphery. The strong association between a number of human autoimmune diseases (type 1 diabetes, rheumatoid arthritis, and multiple sclerosis) and certain HLA-DR/DQ alleles suggests that it may be possible to alter pathological autoimmune responses by deliberate introduction of autoantigenic peptides in a "tolerogenic" manner. Since there are likely to be differences in epitope selection and epitope spreading in different patients over time, this approach requires identification of all the immunogenic CD4+ T-cell epitopes (dominant, subdominant, or cryptic) of an autoantigen which elicit T-cell responses restricted to the HLA-DR/DQ alleles predisposing to these autoimmune diseases. This paper describes a new approach for the identification of immunogenic peptide epitopes of human autoantigenic proteins using HLA-DR and DQ transgenic mice. These mice are engineered to select a full TCR repertoire which can identify immunogenic peptide epitopes similar or identical to human subjects of the same HLA-DR/DQ genotype. This experimental system also allows comparison of autoantigenic immune responses restricted to disease-susceptible and disease-resistant HLA-DR/DQ alleles.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation
  • Autoantigens / immunology*
  • Epitopes*
  • HLA-D Antigens / genetics
  • HLA-D Antigens / immunology*
  • HLA-DQ Antigens / genetics
  • HLA-DQ Antigens / immunology
  • HLA-DR4 Antigen / genetics
  • HLA-DR4 Antigen / immunology
  • Immunodominant Epitopes
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell

Substances

  • Autoantigens
  • Epitopes
  • HLA-D Antigens
  • HLA-DQ Antigens
  • HLA-DQ8 antigen
  • HLA-DR4 Antigen
  • Immunodominant Epitopes
  • Receptors, Antigen, T-Cell