T cell response to two immunodominant proteolipid protein (PLP) peptides in multiple sclerosis patients and healthy controls.
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system in which autoimmune T lymphocytes reacting with myelin antigens are believed to play a pathogenic role. Since HLA binding is involved in the selection of T cell responses, we have examined PLP peptide binding to HLA DR2, an HLA allele frequently found in MS patients. Both PLP 40-60 and PLP 89-106 show significant, high affinity binding to HLA DR2. We then tested whether responses to PLP peptides 40-60 and 89-106 are elevated in multiple sclerosis patients compared to matched controls. We also analysed T cell responses to MBP 87-106, which is considered to be the immunodominant region of MBP in humans. Here we demonstrate heterogenous T cell responses to PLP 40-60, PLP 89-106 and MBP 87-106 in both MS patients and controls. The overall number of TCL and the HLA restriction of those TCL did not vary significantly in the two groups. PLP 40-60 specific cytolytic TCL were increased in MS patients, whereas healthy controls had increased percentages of cytolytic TCL responding to PLP 89-106 and MBP 87-106. Although the data presented here shows heterogenous responses in T cell numbers, differences in numbers and specificity of cytolytic cells could be involved in the pathogenesis of autoimmune demyelinating disease.
Pelfrey
C M
CM
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Tranquill
L R
LR
Vogt
A B
AB
McFarland
H F
HF
D000595:Amino Acid Sequence; D000917:Antibody Formation; D001667:Binding, Competitive; D016022:Case-Control Studies; D006684:HLA-DR Antigens / Q000097:blood; D006801:Humans; D016056:Immunodominant Epitopes; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology*; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D009479:Neuropeptides / Q000276:immunology*; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*
D006684:HLA-DR Antigens; D016056:Immunodominant Epitopes; D018991:Myelin Proteolipid Protein; D009479:Neuropeptides