Allogenic MHC class II determinant(s) in MRL/Ipr autoimmune disease-prone mice. Unusual expression of an L1 transposable element creates molecular mimicry.
In some aged MRL/Ipr autoimmune disease-prone mice, unexpected reactivity has been observed between lymphoid cells and mAb or polyclonal antibodies directed against the A beta d class II chain of the MHC. However, Southern blot analysis of their genomic DNA, using different class I and class II MHC-specific probes, confirmed their inbred character and their H-2k genotype. In this study, immunoprecipitation experiments with an anti-A beta d mAb indicated that the 45 (and 12)-kD molecule(s) recognized by an anti-A beta d mAb differed from a class II chain. After specific antibody screening of a lambda gt11 expression library constructed with MRL/Ipr "A beta d-positive" lymphoid cells, we cloned cDNA that share sequences with high homology (> 80%) to the 3' end of a 7-kb L1Md (L1) element propagated in the mouse genome via retrotransposition. Northern blot analysis showed an overtranscription of these L1 sequences in the MRL/Ipr spleen cells used for the construction of the cDNA library, in comparison to the MRL ancestor strains. Therefore, the autoimmune MRL/Ipr strain could express a translation product of L1 open reading frame 2, which mimics a "highly antigenic" epitope of an allogenic MHC class II Ag.
Bobé
P
P
INSERM U267, Groupe Hospitalier Paul-Brousse, Villejuif, France.
Benihoud
K
K
Kiger
N
N
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification; D004251:DNA Transposable Elements; D000939:Epitopes / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000032:analysis
D004251:DNA Transposable Elements; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D004247:DNA