Role of mouse and human class II transgenes in susceptibility to and protection against mouse autoimmune nhyroiditis

Yi Chi M. Kong, Chella S. David, Lesley C. Lomo, Brian E. Fuller, Reinhard W. Motte, Alvaro A. Giraldo

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Abstract

Mouse experimental autoimmune thyroiditis (EAT), a model for Hashimoto's thyroiditis, is induced by immunising with mouse thyroglobulin (MTg). To study the extent of H2A involvement in EAT, we introduced AaAb genes from susceptible k mice into resistant or intermediately susceptible strains which do not express H2E molecules. Thyroiditis was severe in resistant B10.M (H2(f)) mice carrying the double transgene Aa(k)Ab(k). Likewise, thyroid infiltration was significantly extended in intermediate B10.Q (H2(q)) mice with the same transgene. To examine the effect of H2E molecules in the presence of H2A-mediated susceptibility, we introduced an Ea(k) transgene into E- B10.S mice to express the Eβs molecule and observed significant reduction in EAT severity in B10.S(E+) mice. On the other hand, the presence of an Eb(d) transgene in B10.RQB3 (H2A(q)) mice resulting in the expression of H2Eβ(d) molecules did not alter EAT susceptibility, suggesting a role for Eb gene polymorphism in protection against EAT. We have shown recently that the HLA-DRB1*0301 (DR3) transgene conferred EAT susceptibility to B10.M as well as class II-negative B10.Ab(o) mice. However, we report here that the HLA-DQB1 *0601 (DQ6b) transgene in B10.M or HLA-DQA1 *0301/DQB1 *0302 (DQ8) transgene in class II-negative Ab(o) mice did not. These studies show the differential effects of class II molecules on EAT induction. Susceptibility can be determined when class II molecules from a single locus, H2A or HLA-DQ, are examined in transgenic mice, but the overall effect may depend upon the presence of both class II molecules H2A and H2E in mice and HLA-DQ and HLA-DR in humans.

Original languageEnglish (US)
Pages (from-to)312-317
Number of pages6
JournalImmunogenetics
Volume46
Issue number4
DOIs
StatePublished - Aug 13 1997

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ASJC Scopus subject areas

  • Immunology
  • Genetics

Cite this

Kong, Y. C. M., David, C. S., Lomo, L. C., Fuller, B. E., Motte, R. W., & Giraldo, A. A. (1997). Role of mouse and human class II transgenes in susceptibility to and protection against mouse autoimmune nhyroiditis. Immunogenetics, 46(4), 312-317. https://doi.org/10.1007/s002510050277