'Lupus-prone' mice are susceptible to organ-specific autoimmune disease, experimental allergic encephalomyelitis.
Immunization with the multideterminant autoantigen myelin basic protein (MBP) causes experimental allergic encephalomyelitis (EAE), a T-cell-mediated autoimmune disease that serves as a model for multiple sclerosis (MS). MBP peptides Ac1-11 and p35-47 induce potent EAE in mice of the H-2u haplotype. T cells specific for Ac1-11 predominantly utilize one T-cell receptor (TCR) V beta gene segment, V beta 8.2. All T-cell clones and hybridomas analyzed, regardless of TCR V beta usage, utilize D beta 2 and J beta 2 elements. The NZW mouse strain (H-2z), which contributes to the spontaneous 'lupus-like' illness in (NZB x NZW)F1 mice, has a genomic deletion encompassing D beta 2 and J beta 2 gene segments. The NZW strain expresses class II (I-A and I-E) genes which share identical sequences with H-2u class II. We investigated whether these strains are susceptible to EAE induced with intact MBP and known encephalitogenic MBP peptides. In vitro analysis demonstrated that NZW antigen-presenting cells (APC) can present MBP and MBP peptide Ac1-11 to an encephalitogenic T-cell clone derived from an H-2u mouse, confirming the functional identity of NZW class-II (I-A) molecules with their respective H-2u class-II gene products. In vivo results demonstrated that NZW and (NZB x NZW)F1 mice are susceptible to EAE induced with intact MBP and Ac1-11. MBP p35-47 caused EAE in (NZB x NZW)F1 mice, which express alleles for both the normal (NZB) TCR beta-gene locus, and the abnormal (NZW) TCR beta-gene locus containing the J beta 2 deletion.(ABSTRACT TRUNCATED AT 250 WORDS)
Zamvil
S S
SS
Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Mass 02115.
al-Sabbagh
A
A
Nelson
P A
PA
Kaul
D
D
Charles
M S
MS
Mitchell
D J
DJ
Steinman
L
L
Weiner
H L
HL
Kuchroo
V K
VK
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006183:H-2 Antigens; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006183:H-2 Antigens; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta