Inhibitory peptide analogs derived from a major uveitogenic epitope protect from antiretinal autoimmunity by inducing type 2 and regulatory T cells
| Autor: | Chi-Chao Chan, Mary J. Mattapallil, Lizette M. Cortes, Phyllis B. Silver, Dror Luger, Dody Avichezer, Rachel R. Caspi |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Adoptive cell transfer
Translational and Clinical Reports Immunology Molecular Sequence Data Autoimmunity Lymphocyte proliferation Biology medicine.disease_cause Lymphocyte Activation T-Lymphocytes Regulatory Epitope Retina Immune tolerance Autoimmune Diseases Uveitis Mice Structure-Activity Relationship Antigen medicine Immune Tolerance Immunology and Allergy Animals Amino Acid Sequence Immunogenicity Cell Biology Molecular biology Adoptive Transfer eye diseases Delayed hypersensitivity Models Animal Cytokines Peptides |
| Zdroj: | Journal of leukocyte biology. 84(2) |
| ISSN: | 0741-5400 |
| Popis: | We identified inhibitory peptide ana- logs (IPAs), capable of immunomodulating exper- imental autoimmune uveitis (EAU), induced in B10.RIII mice by immunization with the retinal antigen interphotoreceptor-binding protein in CFA. Alanine-substituted peptides of the major pathogenic epitope, residues 161-180, were syn- thesized. They were tested for immunogenicity, cross-reactivity with the native 161-180 epitope, pathogenicity, and ability to prevent EAU when given in IFA before EAU challenge with native murine (m)161-180. Two peptides, 169A and 171A, were unable to elicit disease but cross-re- acted with m161-180 by lymphocyte prolifera- tion. Mice pretreated with either of the substituted peptides failed to develop EAU after challenge with the native epitope, m161-180, and had reduced cellular responses by lymphocyte proliferation and by delayed hypersensitivity. Their cytokine re- sponse profile to m161-180 showed reduced anti- gen-specific IFN- and IL-17, whereas IL-4, IL-5, IL-10, and IL-13 from IPA-protected mice were increased, and serum antibody titers to m161-180 revealed reduced IgG2a and elevated IgG1 iso- types, suggesting a Th2 shift in the response. Pro- tection was transferable with lymphoid cells from protected donors to naive recipients, who were subsequently immunized for EAU. Thus, IPA pre- treatment prevents induction of EAU by skewing the response to a subsequent uveitogenic challenge with the native peptide to a nonpathogenic pheno- type, as well as by eliciting transferable regulatory cells. J. Leukoc. Biol. 84: 577-585; 2008. |
| Databáze: | OpenAIRE |
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