April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
HLA Class II Specific Epitopes of Retinal Arrestin Are Uveitogenic in the ‘Humanized’ Mouse Model of EAU
Author Affiliations & Notes
  • M. J. Mattapallil
    Laboratory of Immunoregulation, National Eye Institute, Bethesda, Maryland
  • P. Silver
    Laboratory of Immunoregulation, National Eye Institute, Bethesda, Maryland
  • J. Mattapallil
    Dept. Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, Maryland
  • Z. Karabekian
    Laboratory of Immunoregulation, National Eye Institute, Bethesda, Maryland
  • H. McDowell
    Department of Ophthalmology, University of Florida, Gainesville, Florida
  • C.-C. Chan
    Laboratory of Immunoregulation, National Eye Institute, Bethesda, Maryland
  • E. James
    Tetramer Facility, Benaroya Research Institute at Virginia Mason, Seattle, Washington
  • W. Kwok
    Tetramer Facility, Benaroya Research Institute at Virginia Mason, Seattle, Washington
  • C. David
    Department of Immunology, Mayo Clinic, Rochester, Minnesota
  • R. R. Caspi
    Laboratory of Immunology, National Eye Inst/NIH, Bethesda, Maryland
  • Footnotes
    Commercial Relationships  M.J. Mattapallil, None; P. Silver, None; J. Mattapallil, None; Z. Karabekian, None; H. McDowell, None; C.-C. Chan, None; E. James, None; W. Kwok, None; C. David, None; R.R. Caspi, None.
  • Footnotes
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Investigative Ophthalmology & Visual Science April 2010, Vol.51, 5163. doi:
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      M. J. Mattapallil, P. Silver, J. Mattapallil, Z. Karabekian, H. McDowell, C.-C. Chan, E. James, W. Kwok, C. David, R. R. Caspi; HLA Class II Specific Epitopes of Retinal Arrestin Are Uveitogenic in the ‘Humanized’ Mouse Model of EAU. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5163.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Autoimmune uveitis affects 150,000 Americans annually and is a leading cause of blindness. Pathogenesis is thought to involve T cell mediated responses to retinal proteins, such as retinal arrestin (S-Ag). Susceptibility to autoimmune uveitis is strongly associated with HLA class I and class II alleles. The objective of this study was to define the epitopes that might be pathogenic in the context of different HLA class II molecules.

Methods: : Experimental autoimmune uveitis (EAU) was induced in the ‘humanized’ mouse model, transgenic for different HLA class II alleles, using S-Ag. Synthetic peptides based on the amino acid sequence of S-Ag protein were used to identify immunodominant and pathogenic epitopes specific to each HLA class II alleles. HLA class II tetramer loaded with allele specific uveitogenic epitopes of S-Ag was used to identify and isolate pathogenic CD4 positive T cells.

Results: : We have identified permissive and non-permissive alleles of the HLA-DR and -DQ genes and characterized allele-specific uveitogenic epitopes. The sequences of these epitopes overlap with some of the previously identified peptides of S-Ag (M and N), which elicit memory responses in lymphocytes of uveitis patients. HLA-DR restricted S-Ag specific CD4+ T cells could be detected in blood and draining lymph nodes of immunized mice using HLA class II tetramers.

Conclusions: : Our results demonstrate that HLA class II tetramers can be used to detect and isolate antigen specific T cells in uveitis patients. Our data provide new insights into the pathogenesis of human uveitis, and may help in the development of antigen specific therapies.

Keywords: uveitis-clinical/animal model • genetics • retina 
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