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Molecular and genetic requirements for preferential recruitment of TCRBV8S2+ T cells in Lewis rat experimental autoimmune encephalomyelitis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Lobell / Kämpe)
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1998 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 160, no 2, 681-690 p.Article in journal (Other academic) Published
Abstract [en]

The underlying mechanisms behind the preferential expression of select TCRBV products in certain autoimmune illnesses, such as multiple sclerosis and some models of experimental autoimmune encephalomyelitis (EAE), have principally remained enigmatic. In this study, we examined the mutual role of nonself- vs self-origin of antigenic myelin basic protein (MBP) peptides and given MHC haplotypes in relation to the relative frequency of activated TCRBV8S2+ T lymphocytes in the Lewis (LEW) rat EAE model. Inbred MHC (RT1) congenic LEW rats (LEW (RT1l), LEW.1AV1 (RT1av1), and LEW.1W (RT1u)) were immunized with the 63 to 88 peptide of the guinea pig MBP (MBPGP63-88). Additionally, LEW rats were immunized with the corresponding autologous rat sequence (MBPRAT63-88). Although EAE ensued in all MBP peptide/LEW rat strain combinations, only LEW rats immunized with the heterologous MBPGP63-88 peptide elicited T cell responses encompassing a bias toward TCRBV8S2 expression, as determined by flow cytometric analyses. Reduction of TCRBV8S2+ T cells led to mitigation of disease severity in LEW rats immunized with MBPGP63-88, but not with MBPRAT63-88, indicating that critical encephalitogenic characteristics are associated with this T cell subset. We conclude that the preferential recruitment of TCRBV8S2+ T cells in the LEW rat EAE model is due to selective, high-avidity recognition of the nonself-MBPGP63-88 in the context of the RT1.Bl molecule. This inference lends support to the notion that the highly restricted TCR repertoire of the self-MBP-reactive T cells in certain genetically predisposed multiple sclerosis patients may have its source in a multistep molecular mimicry event.

Place, publisher, year, edition, pages
1998. Vol. 160, no 2, 681-690 p.
Keyword [en]
Amino Acid Sequence, Animals, Binding Sites/genetics/immunology, Cell Division/genetics/immunology, Cell Movement/genetics/*immunology, Central Nervous System/immunology, Cross Reactions, Encephalomyelitis; Autoimmune; Experimental/blood/*genetics/*immunology, Histocompatibility Antigens/genetics/metabolism, Lymphocyte Activation/genetics, Lymphocyte Count, Lymphocyte Depletion, Male, Molecular Sequence Data, Myelin Basic Proteins/immunology/metabolism, Peptide Fragments/immunology/metabolism, Rats, Rats; Inbred Lew, Receptors; Antigen; T-Cell; alpha-beta/*genetics/*immunology, Research Support; Non-U.S. Gov't, T-Lymphocyte Subsets/*immunology/metabolism
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Medical and Health Sciences
URN: urn:nbn:se:uu:diva-70104PubMedID: 9551903OAI: oai:DiVA.org:uu-70104DiVA: diva2:98015
Available from: 2005-04-15 Created: 2005-04-15 Last updated: 2010-07-16Bibliographically approved

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