Title
EBV-induced expression and HLA-DR-restricted presentation by human B cells of alphab-crystallin, a candidate autoantigen in multiple sclerosis
Author
TNO Preventie en Gezondheid
van Sechel, A.C.
Bajramovic̀, J.J.
van Stipdonk, M.J.B.
Persoon-Deen, C.
Geutskens, S.B.
van Noort, J.M.
Publication year
1999
Abstract
The development of multiple sclerosis is most likely influenced by autoimmune responses to central nervous system myelin proteins as well as by infections with common viruses such as EBV and human herpesvirus-6. However, much remains to be established on how these factors interact. In this study, we show that upon EBV infection, human B cells start to express alphaB- crystallin, a small stress protein that was identified previously as an immunodominant Ag of CNS myelin in multiple sclerosis patients. EBV-induced expression of alphaB-crystallin in B cells leads to HLA-DR-restricted presentation of the protein and to activation of proinflammatory alphaB- crystallin-specific Th cells. While alphaB-crystallin is present in EBV-infected human B cells, the protein is absent from human lymphoid tissues under normal conditions. This is in sharp contrast to other stress proteins such as heat- shock protein (hsp)27 and hsp60 that are ubiquitously expressed in these tissues. In addition, the absence of alphaB-crystallin from lymphoid tissues in humans is unique as compared with other mammals. All other species examined, including rodents, sheep, and primates, showed constitutive expression of alphaB-crystallin in secondary lymphoid tissues and sometimes even in the thymus. Since constitutive lymphoid expression most likely results in immunologic tolerance, such a state of tolerance to alphaB-crystallin can be expected for all of these species, but not for humans. When taken together, our data provide evidence for a novel mechanism by which common viral infections can trigger myelin-directed autoimmunity in a way that is unique for humans.
Subject
Animals
Antigen Presentation
Autoantigens
B-Lymphocyte Subsets
Cell Line, Transformed
Cell Transformation, Viral
Crystallins
Epitopes, T-Lymphocyte
Female
Heat-Shock Proteins
Herpesvirus 4, Human
HLA-DR Antigens
Humans
Lymphocyte Activation
Lymphoid Tissue
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred Strains
Multiple Sclerosis
Primates
Rats
Rats, Inbred BN
Rats, Inbred Lew
Sheep
T-Lymphocyte Subsets
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TNO identifier
234901
ISSN
0022-1767
Source
Journal of Immunology, 162 (162), 129-135
Document type
article