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The human leukocyte antigen complex and chronic ocular inflammatory disorders
1Department of Veteran Affairs Medical Center, Department of Medicine, Oregon Health Sciences University, Portland 97201, USA. daveym@ohsu.edu
Insights
Human leukocyte antigen (HLA) gene products are crucial for immune function and can be linked to chronic ocular inflammatory diseases. Their role in T-cell development and peptide presentation may contribute to autoimmunity and disease.
Area of Science:
- Immunology
- Genetics
- Ophthalmology
Background:
- The human leukocyte antigen (HLA) complex plays a critical role in immune system regulation.
- Specific HLA alleles are frequently associated with chronic ocular inflammatory diseases.
- Understanding normal HLA function offers insights into disease mechanisms.
Purpose of the Study:
- To review the function of human leukocyte antigen (HLA) gene products.
- To explore their role in normal immune function, ocular inflammation, and autoimmunity models.
Main Methods:
- Literature review of recent scientific reports.
Main Results:
- HLA molecules shape the developing T-cell repertoire, ensuring self-tolerance.
- In the periphery, HLA molecules present peptides to T cells, mediating effector functions.
- Pathologic T-cell responses can arise from peptide-HLA interactions, as seen in autoimmunity models.
- Herpes stromal keratitis models illustrate the interplay of self-tolerance, infection, and molecular mimicry.
Conclusions:
- HLA gene products may drive chronic inflammatory disorders.
- This can occur through presenting disease-inducing peptides or fostering autoreactive T-cell repertoires.
- Molecular mimicry is a potential mechanism linking HLA to autoimmunity.
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.