Vaccination with peptides from MHC class II beta chain hypervariable region causes allele-specific suppression of EAE.
In our earlier studies we showed that successful immunotherapy of EAE in SJL/J mice can be achieved either by the use of antibodies to MHC class II antigens or by vaccination with synthetic peptide analogs of the beta chain of MHC class II molecules. We proposed that inhibition of EAE following vaccination with synthetic peptides derived from the beta chain of mouse I-A, was in part due to the generation of auto-anti-MHC class II antibodies that interfered with T cell sensitization. In our present study we show that suppression of EAE following vaccination results in poor sensitization of MBP reactive T cells, and that the lack of immune response is allele-specific. In F1(SJL(I-AS) x Balb/cI-Ad) mice, in which susceptibility to EAE is linked closely to the I-AS allele, vaccination with peptides from beta chain of I-AS results in inhibition of proliferative response to MBP and prevents the development of EAE. Vaccination with peptide from the beta chain of I-Ad did not affect either the development of immune response to MBP or the induction of EAE, indicating allele-specific suppression. Since global immunosuppression is not induced by vaccination with I-A peptides, we propose that this strategy can be extended to human autoimmune diseases wherein a clear association between certain MHC class II alleles and autoimmune disease is evident.
Bright
J J
JJ
Multiple Sclerosis Research Laboratory, Vanderbilt Stallworth Rehab Hospital, Nashville, TN 37212, USA.
Topham
D J
DJ
Nag
B
B
Lodge
P A
PA
Sriram
S
S
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D003207:Conalbumin / Q000276:immunology / Q000494:pharmacology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D007135:Immunoglobulin Variable Region / Q000276:immunology / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D014611:Vaccination
D000949:Histocompatibility Antigens Class II; D007135:Immunoglobulin Variable Region; D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D003207:Conalbumin