Differing MHC class I requirements for induction and propagation of experimental systemic lupus erythematosus

D S Singer; H Zinger; L D Kohn; E Mozes

doi:10.1002/(SICI)1521-4141(199907)29:07<2259::AID-IMMU2259>3.0.CO;2-1

Differing MHC class I requirements for induction and propagation of experimental systemic lupus erythematosus

Eur J Immunol. 1999 Jul;29(7):2259-68. doi: 10.1002/(SICI)1521-4141(199907)29:07<2259::AID-IMMU2259>3.0.CO;2-1.

Authors

D S Singer¹, H Zinger, L D Kohn, E Mozes

Affiliation

¹ Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Dinah.Singer@nih.gov

Abstract

Mice deficient in beta2-microglobulin expression are resistant to the induction of experimental systemic lupus erythematosus (SLE). The present studies were designed to identify the beta2-microglobulin-dependent cell surface molecule(s) that confers sensitivity to experimental SLE, and to determine its role in disease development. We report hat mice lacking the transporter associated with antigen presentation (TAP-/-) were also resistant to disease, whereas CD1-/- and CD8-/- mice were susceptible; susceptibility also did not correlate with neonatal Fc receptor or HEPH expression. These data indicate that disease susceptibility is determined by expression of MHC class I. Furthermore, by analyzing both adoptive transfer and radiation bone marrow chimeras, we demonstrate that MHC class I expression is necessary for propagation of disease, but not for induction of pathogenic cells.

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 2
ATP-Binding Cassette Transporters / genetics
ATP-Binding Cassette Transporters / immunology
ATP-Binding Cassette Transporters / metabolism
Animals
Antigens, CD1 / genetics
Antigens, CD1 / metabolism
Bone Marrow / immunology
Bone Marrow / pathology
CD8 Antigens / genetics
CD8 Antigens / metabolism
Disease Models, Animal
Female
Histocompatibility Antigens Class I / metabolism*
Histocompatibility Antigens Class II / genetics
Histocompatibility Antigens Class II / metabolism
Kidney / immunology
Kidney / pathology
Lupus Erythematosus, Systemic / etiology*
Lupus Erythematosus, Systemic / genetics
Lupus Erythematosus, Systemic / immunology*
Lymphoid Tissue / immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Radiation Chimera
beta 2-Microglobulin / deficiency
beta 2-Microglobulin / genetics
beta 2-Microglobulin / immunology

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 2
ATP-Binding Cassette Transporters
Antigens, CD1
CD8 Antigens
Histocompatibility Antigens Class I
Histocompatibility Antigens Class II
TAP1 protein, human
Tap1 protein, mouse
beta 2-Microglobulin