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

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 PLP91-110 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.

Original languageEnglish (US)
Pages (from-to)280-290
Number of pages11
JournalEuropean Journal of Immunology
Volume34
Issue number1
DOIs
StatePublished - Jan 2004

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Proteolipids
T-Lymphocyte Epitopes
Autoimmune Experimental Encephalomyelitis
Transgenic Mice
Multiple Sclerosis
HLA-DR2 Antigen
HLA-DR3 Antigen
Autoantigens
Proteins
Genes
MHC Class II Genes
Linkage Disequilibrium
Demyelinating Diseases
Epitopes
Cytokines
Amino Acids
Peptides

Keywords

  • EAE
  • Epitope
  • MHC
  • MS
  • Proteolipid protein (PLP)
  • Transgenic

ASJC Scopus subject areas

  • Immunology

Cite this

Identification of T cell epitopes on human proteolipid protein and induction of experimental autoimmune encephalomyelitis in HLA class II-transgenic mice. / Mangalam, Ashutosh K.; Khare, Meenakshi; Krco, Christopher; Rodriguez, Moses; David, Chella.

In: European Journal of Immunology, Vol. 34, No. 1, 01.2004, p. 280-290.

Research output: Contribution to journalArticle

Mangalam, Ashutosh K. ; Khare, Meenakshi ; Krco, Christopher ; Rodriguez, Moses ; David, Chella. / Identification of T cell epitopes on human proteolipid protein and induction of experimental autoimmune encephalomyelitis in HLA class II-transgenic mice. In: European Journal of Immunology. 2004 ; Vol. 34, No. 1. pp. 280-290.
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