Identification of an epitope derived from human proteolipid protein that can induce autoreactive CD8+ cytotoxic T lymphocytes restricted by HLA-A3: evidence for cross-reactivity with an environmental microorganism.
The demyelination process that occurs in the central nervous system (CNS) of patients with multiple sclerosis (MS) is in part due to an inflammatory response in which CD4+ and CD8+ T cells and macrophages infiltrate white matter. In this study, we have identified a peptide sequence derived from the CNS-specific myelin protein proteolipid protein (PLP) which could bind to HLA-A3 and induce a HLA-A3-restricted CD8+ CTL response from HLA-A3+ donors. These PLP peptide-specific CTL could lyse HLA-A3+ target cells pulsed with a homologous peptide derived from the CRM1 protein of Saccharomyces cerevisae. These findings demonstrate the immunogenic potential of a PLP-derived peptide for generation of autoreactive HLA-A3-restricted CD8+ CTL, and further show that these CTL can be activated by a peptide derived from a common environmental microorganism.
Honma
K
K
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Parker
K C
KC
Becker
K G
KG
McFarland
H F
HF
Coligan
J E
JE
Biddison
W E
WE
D000328:Adult; D001059:Apoproteins / Q000276:immunology*; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D003429:Cross Reactions; D016207:Cytokines / Q000378:metabolism; D000939:Epitopes; D005260:Female; D005656:Fungal Proteins / Q000276:immunology; D015791:HLA-A3 Antigen / Q000276:immunology*; D006801:Humans; D028884:Karyopherins; D008297:Male; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D018160:Receptors, Cytoplasmic and Nuclear; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000097606:Exportin 1 Protein
D001059:Apoproteins; D016207:Cytokines; D000939:Epitopes; D005656:Fungal Proteins; D015791:HLA-A3 Antigen; D028884:Karyopherins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein