HLA-DRB5*0101 and -DRB1*1501 expression in the multiple sclerosis-associated HLA-DR15 haplotype.

Abstract

The HLA region, and particularly the DR15 haplotype (containing the two DRB* genes DRB1*1501 and DRB5*0101 and the tightly linked DQ alleles DQA*0102 and DQB1*0602, which together form the DQw6 molecule) in Caucasians, shows the strongest genetic association with multiple sclerosis (MS). In the DR15 haplotype, two beta-chains HLA-DRB1*1501 and -DRB5*0101 are co-expressed resulting in two different surface HLA-DR alphabeta heterodimers, DR2b and DR2a. Most previous studies focused on DRB1*1501, however, both DR2a and DR2b may contribute to MS pathogenesis via antigen presentation to myelin-specific T lymphocytes. We therefore analyzed the expression of the two DR15 genes in various antigen presenting cells (APCs), central nervous system and thymic tissues. Transcript levels were higher for DRB5*0101 in all cell types and tissues. Both HLA-DR heterodimers were expressed at significant levels on the cell surface, where they showed a differential expression pattern in different APCs. They were similarly regulated after stimulation with interferon-gamma and interleukin-4. Finally, immunohistochemistry experiments indicated that both molecules were expressed in thymic tissue. Our results encourage future research to investigate the potential functional relevance of both genes for the pathogenesis of MS.

• Authors: Elisabetta Prat, Utano Tomaru, Lidia Sabater, Deric M Park, Rebekah Granger, Niels Kruse, Joan M Ohayon, Maria P Bettinotti, Roland Martin
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 167 Issue 1-2 Pg. 108-19 (Oct 2005) ISSN: 0165-5728 [Print] Netherlands
• PMID: 16111772 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-DR Antigens
• HLA-DR Serological Subtypes
• HLA-DR15 antigen
• HLA-DRB1 Chains
• HLA-DRB1*15:01 antigen
• HLA-DRB5 Chains
• RNA, Messenger
• Interferon-beta

Topics

• Cells, Cultured
• Central Nervous System (metabolism, pathology)
• Dendritic Cells (drug effects, metabolism)
• Female
• Flow Cytometry (methods)
• Fluorescent Antibody Technique (methods)
• Gene Expression (drug effects, physiology)
• HLA-DR Antigens (genetics, metabolism)
• HLA-DR Serological Subtypes
• HLA-DRB1 Chains
• HLA-DRB5 Chains
• Haplotypes
• Humans
• Interferon-beta (pharmacology)
• Lymphocytes (cytology, drug effects, metabolism)
• Male
• Multiple Sclerosis (classification, genetics, metabolism)
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• Statistics, Nonparametric
• Thymus Gland (metabolism, pathology)
• Transfection (methods)