Abstract
Using single H2 and HLA class II transgenic mice, in the absence of endogenous H2 class II molecules, we have studied the permissiveness of class II molecules for experimental autoimmune thyroiditis (EAT). Resistant strains expressing susceptible class II molecules, H2Ak or HLA-DR3, developed EAT, clearly demonstrating the importance of class II gene inheritance. Polymorphism for HLA-DRB1 was observed, as DR3, but not DR2 or DR4, molecules were permissive for EAT induction with either mouse (m) or human (h) thyroglobulin (Tg). HLA-DQ polymorphism was also detectable, as hTg-induced EAT developed in ·DQ8+, but not DQ6+, mice. Class II gene interactions leading to reduced EAT severity were observed in H2 transgenic mice, when H2E transgene was expressed in H2A+ mice or H2A molecules were introduced into our novel H2A-E+ transgenic model. Similarly, in DR3+ mice, only the DQ8 transgene reduced EAT severity, depending on both background genes (C57BL/10 or NOD) and Tg species. Based on computer-predicted, class II-binding motifs, potential pathogenic Tg peptides, either unique to hTg (H2A-E+ model) or shared between mTg and hTg (HLA-DR3+ model), were identified. We have also developed a Graves' disease model by immunizing DR3+ mice with TSH receptor DNA. Thus, transgenic models are excellent tools to study human autoimmune thyroid diseases in the context of murine EAT.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 397-404 |
| Number of pages | 8 |
| Journal | Autoimmunity |
| Volume | 36 |
| Issue number | 6-7 |
| DOIs | |
| State | Published - Sep 2003 |
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Keywords
- Autoimmune thyroiditis
- Autoimmunity
- Class II interactions
- Graves' disease model
- H2 transgenes
- HLA transgenes
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
HLA and H2 class II transgenic mouse models to study susceptibility and protection in autoimmune thyroid disease. / Kong, Yi Chi M; Flynn, Jeffrey C.; Wan, Qiang; David, Chella S.
In: Autoimmunity, Vol. 36, No. 6-7, 09.2003, p. 397-404.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - HLA and H2 class II transgenic mouse models to study susceptibility and protection in autoimmune thyroid disease
AU - Kong, Yi Chi M
AU - Flynn, Jeffrey C.
AU - Wan, Qiang
AU - David, Chella S.
PY - 2003/9
Y1 - 2003/9
N2 - Using single H2 and HLA class II transgenic mice, in the absence of endogenous H2 class II molecules, we have studied the permissiveness of class II molecules for experimental autoimmune thyroiditis (EAT). Resistant strains expressing susceptible class II molecules, H2Ak or HLA-DR3, developed EAT, clearly demonstrating the importance of class II gene inheritance. Polymorphism for HLA-DRB1 was observed, as DR3, but not DR2 or DR4, molecules were permissive for EAT induction with either mouse (m) or human (h) thyroglobulin (Tg). HLA-DQ polymorphism was also detectable, as hTg-induced EAT developed in ·DQ8+, but not DQ6+, mice. Class II gene interactions leading to reduced EAT severity were observed in H2 transgenic mice, when H2E transgene was expressed in H2A+ mice or H2A molecules were introduced into our novel H2A-E+ transgenic model. Similarly, in DR3+ mice, only the DQ8 transgene reduced EAT severity, depending on both background genes (C57BL/10 or NOD) and Tg species. Based on computer-predicted, class II-binding motifs, potential pathogenic Tg peptides, either unique to hTg (H2A-E+ model) or shared between mTg and hTg (HLA-DR3+ model), were identified. We have also developed a Graves' disease model by immunizing DR3+ mice with TSH receptor DNA. Thus, transgenic models are excellent tools to study human autoimmune thyroid diseases in the context of murine EAT.
AB - Using single H2 and HLA class II transgenic mice, in the absence of endogenous H2 class II molecules, we have studied the permissiveness of class II molecules for experimental autoimmune thyroiditis (EAT). Resistant strains expressing susceptible class II molecules, H2Ak or HLA-DR3, developed EAT, clearly demonstrating the importance of class II gene inheritance. Polymorphism for HLA-DRB1 was observed, as DR3, but not DR2 or DR4, molecules were permissive for EAT induction with either mouse (m) or human (h) thyroglobulin (Tg). HLA-DQ polymorphism was also detectable, as hTg-induced EAT developed in ·DQ8+, but not DQ6+, mice. Class II gene interactions leading to reduced EAT severity were observed in H2 transgenic mice, when H2E transgene was expressed in H2A+ mice or H2A molecules were introduced into our novel H2A-E+ transgenic model. Similarly, in DR3+ mice, only the DQ8 transgene reduced EAT severity, depending on both background genes (C57BL/10 or NOD) and Tg species. Based on computer-predicted, class II-binding motifs, potential pathogenic Tg peptides, either unique to hTg (H2A-E+ model) or shared between mTg and hTg (HLA-DR3+ model), were identified. We have also developed a Graves' disease model by immunizing DR3+ mice with TSH receptor DNA. Thus, transgenic models are excellent tools to study human autoimmune thyroid diseases in the context of murine EAT.
KW - Autoimmune thyroiditis
KW - Autoimmunity
KW - Class II interactions
KW - Graves' disease model
KW - H2 transgenes
KW - HLA transgenes
UR - http://www.scopus.com/inward/record.url?scp=0141815956&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0141815956&partnerID=8YFLogxK
U2 - 10.1080/08916930310001603028
DO - 10.1080/08916930310001603028
M3 - Article
C2 - 14669947
AN - SCOPUS:0141815956
VL - 36
SP - 397
EP - 404
JO - Autoimmunity
JF - Autoimmunity
SN - 0891-6934
IS - 6-7
ER -