Identification of T cell epitopes on human proteolipid protein and induction of experimental autoimmune encephalomyelitis in HLA class II-transgenic mice

Ashutosh K Mangalam; Meenakshi Khare; Christopher Krco; Moses Rodriguez; Chella David

doi:10.1002/eji.200324597

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Identification of T cell epitopes on human proteolipid protein and induction of experimental autoimmune encephalomyelitis in HLA class II-transgenic mice

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Identification of T cell epitopes on human proteolipid protein and induction of experimental autoimmune encephalomyelitis in HLA class II-transgenic mice

Ashutosh K Mangalam, Meenakshi Khare, Christopher Krco, Moses Rodriguez and Chella David

European journal of immunology, Vol.34(1), pp.280-290

01/2004

DOI: 10.1002/eji.200324597

PMID: 14971054

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Abstract

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the CNS that is associated with HLA class II molecules HLA-DR2, -DR3 and -DR4. Previously, it has been difficult to analyze the role of individual HLA molecules in disease pathogenesis due to heterogeneity of MHC genes, linkage disequilibrium, influence of non-MHC genes and contribution of environment. To overcome some of these problems, we have generated HLA-transgenic (tg) mice to investigate function and interaction of these molecules in disease pathogenesis. To investigate the role of individual HLA class II genes in immune responses to human proteolipid protein (PLP), a candidate autoantigen in MS, mice expressing HLA genes DR2, DR3, DR4 (DRB1*0401 and DRB1*0402), DQ6 and DQ8, lacking endogenous class II molecules were immunized with overlapping peptides of PLP. In all tg mice, the majority of the dominant T cell epitopes were clustered mainly to three region; amino acids 31-70, 91-120 and 178-228, of the PLP molecules. We also identified an encephalitogenic epitope PLP(91-110) that induced clinical EAE in HLA-DR3 tg mice. These tg mice had inflammatory infiltrates classically associated with EAE and showed a Th1 cytokine profile. This humanized mouse model of MS will be valuable in deciphering the role of HLA molecules and autoantigens in MS.

Myelin Proteolipid Protein - immunology

Spinal Cord - metabolism

Cytokines - metabolism

Humans

Encephalomyelitis, Autoimmune, Experimental - immunology

Mice, Transgenic

Brain - metabolism

Animals

Histocompatibility Antigens Class II - immunology

Spinal Cord - pathology

Brain - pathology

Histocompatibility Antigens Class II - metabolism

Mice

Epitopes, T-Lymphocyte - immunology

Histocompatibility Antigens Class II - genetics

Details

Title: Subtitle: Identification of T cell epitopes on human proteolipid protein and induction of experimental autoimmune encephalomyelitis in HLA class II-transgenic mice
Creators: Ashutosh K Mangalam - Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA
Meenakshi Khare
Christopher Krco
Moses Rodriguez
Chella David
Resource Type: Journal article
Publication Details: European journal of immunology, Vol.34(1), pp.280-290
DOI: 10.1002/eji.200324597
PMID: 14971054
NLM abbreviation: Eur J Immunol
ISSN: 0014-2980
eISSN: 1521-4141
Publisher: Germany
Grant note: P01-NS38468 / NINDS NIH HHS AI-14764 / NIAID NIH HHS
Language: English
Date published: 01/2004
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9983905644802771

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