Antigen presentation in uveitis

Shiv A. Prasad, Dale S. Gregerson

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Experimental autoimmune uveoretinitis (EAU) is not only a valuable model for human inflammatory eye diseases, it is also a useful system for studying many aspects of immunobiology. One such aspect is self/non-self discrimination, the ability of the immune system to tolerate self molecules while responding aggressively to foreign antigens. Our laboratory has used EAU to investigate the mechanisms of T cell tolerance to retinal S-antigen (S-Ag). Several mechanisms have been proposed to maintain T cell tolerance to autoantigens, including clonal deletion and clonal anergy. As immunisation with S-Ag or pathogenic peptides activates uveitogenic T cells, tolerance to this autoantigen cannot be due to clonal deletion. Nevertheless, tolerance acts to keep these existing autoreactive T cells in a naive, or innocuous state. Here we suggest a novel mechanism - low-affinity occupancy of the autoantigen-specific T cell receptor (TCR) by self-antigen - that may act in concert with the well-known mechanisms to maintain tolerance to S-Ag in the LEW rat. This model differs from clonal anergy in that the missing antigen-presenting cell (APC) activity is not a co-stimulatory function but a TCR co-ligand that increases the avidity of the interaction between the TCR and its peptide-major histocompatibility complex (MHC) ligand. In the absence of this co-ligand only partial signals are generated through the TCR, leading to incomplete T cell activation. This model was deduced from experiments with T cell lines and hybridomas specific for S-Ag, which showed that: (1) autoreactive T cells required a novel APC function, (2) this novel function was necessary to provide complete TCR engagement, and (3) activation of autoreactive T cells was restricted to specific APC.

Original languageEnglish (US)
Pages (from-to)176-182
Number of pages7
JournalEye
Volume11
Issue number2
DOIs
StatePublished - Jan 1 1997

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Keywords

  • Antigen presentation
  • Autoantigens
  • Immune tolerance
  • Retinitis
  • T lymphocytes

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