M P Davey1, J T Rosenbaum. 1. Department of Veteran Affairs Medical Center, Department of Medicine, Oregon Health Sciences University, Portland 97201, USA. daveym@ohsu.edu
Abstract
PURPOSE: To review the role of gene products from the human leukocyte antigen (HLA) complex in the normal functioning of the immune system, ocular inflammation, and models of autoimmunity. METHOD: A review of recently published reports. RESULTS: Many chronic ocular inflammatory diseases are associated with specific alleles of the HLA complex. Understanding how HLA gene products function normally provides clues to the mechanism of disease associations. In the thymus, these molecules control the shape of the developing T-cell repertoire, leading to self-tolerance. In the periphery, HLA molecules bind and present peptide fragments to T cells, leading to a variety of effector functions. Although effector functions are for the most part beneficial, models are reviewed in which peptide-HLA interactions lead to T-cell responses with pathologic consequences. Herpes stromal keratitis is an informative animal model highlighting the role of self-tolerance, infection, and molecular mimicry in the development of autoimmunity. CONCLUSIONS: Human leukocyte antigen gene products may be associated with chronic inflammatory disorders through the unique presentation of "disease-inducing" peptides or the development of a T-cell repertoire prone to autoreactivity and molecular mimicry.
PURPOSE: To review the role of gene products from the human leukocyte antigen (HLA) complex in the normal functioning of the immune system, ocular inflammation, and models of autoimmunity. METHOD: A review of recently published reports. RESULTS: Many chronic ocular inflammatory diseases are associated with specific alleles of the HLA complex. Understanding how HLA gene products function normally provides clues to the mechanism of disease associations. In the thymus, these molecules control the shape of the developing T-cell repertoire, leading to self-tolerance. In the periphery, HLA molecules bind and present peptide fragments to T cells, leading to a variety of effector functions. Although effector functions are for the most part beneficial, models are reviewed in which peptide-HLA interactions lead to T-cell responses with pathologic consequences. Herpes stromal keratitis is an informative animal model highlighting the role of self-tolerance, infection, and molecular mimicry in the development of autoimmunity. CONCLUSIONS:Human leukocyte antigen gene products may be associated with chronic inflammatory disorders through the unique presentation of "disease-inducing" peptides or the development of a T-cell repertoire prone to autoreactivity and molecular mimicry.
Authors: D J Kilmartin; D Wilson; J Liversidge; A D Dick; J Bruce; R W Acheson; S J Urbaniak; J V Forrester Journal: Br J Ophthalmol Date: 2001-03 Impact factor: 4.638