Characterization of a new, potent, immunopathogenic epitope in S-antigen that elicits T cells expressing Vβ8 and Vα2-like genes

C. F. Merryman, L. A. Donoso, X. Zhang, E. Heber-Katz, D. S. Gregerson

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Experimental autoimmune uveoretinitis (EAU) is a predominantly T cell-mediated autoimmune disease induced in susceptible animals by active immunization with human or bovine retinal S-Ag or by passive transfer of activated S-Ag or peptide-specific CD4+ T cells. During the course of studies aimed at the identification of T cell and B cell recognition sites in bovine and human S-Ag, a new potent uveitogenic region, located near the carboxy terminus of the molecule, was identified and characterized. Analysis of several synthetic peptides from this region showed that a 14 amino acid residue peptide, BSAg339-352, was highly uveitogenic when injected with adjuvants into Lewis rats. A uveitogenic T cell line, R737, was raised by in vitro selection of lymphocytes from animals immunized with peptide BSAg333-352. Northern blot analysis of mRNA from the R737 T cell line was positive for the rat homologs of murine Vβ8 and Vα2 T cell receptor gene probes. Whereas peptide BSAg339-352 defined the pathogenic site, nonpathogenic, proliferative sites were found in close physical association. This region is immediately adjacent to previously characterized pathogenic and proliferative sites contained in residues BSAg352-364. These results, as well as our previous observations, show S-Ag to be a complex molecule with several highly conserved amino acid sequences that can elicit pathogenic T cells with restricted T cell receptor V gene usage capable of active and passive elicitation of experimental autoimmune uveoretinitis.

Original languageEnglish (US)
Pages (from-to)75-80
Number of pages6
JournalJournal of Immunology
Volume146
Issue number1
StatePublished - 1991

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