Blood CD8+ T cell responses against myelin determinants in multiple sclerosis and healthy individuals.
Patients with multiple sclerosis (MS) display significant peripheral blood CD8(+) T cell receptor biases, suggesting clonal selection. Our objective was to identify relevant myelin-derived peptides capable of eliciting responses of fresh blood CD8+ T cells in MS patients. We focused our analysis on the HLA supertypes (HLA-A3, -A2, -B7, -B27, -B44) predominant in a patient cohort. Three myelin protein (MBP, PLP and MOG) sequences were screened for HLA binding motifs and peptides were tested for their binding to HLA molecules. The cellular responses of 27 MS patients and 19 age- and sex-matched healthy controls (HC) were tested in IFN-gamma ELISPOT assays only detecting pre-committed CD8+ T cells. Sixty-nine new epitopes elicited positive responses, with MOG-derived peptides being the most immunogenic and peptides binding to HLA-A3 being the most frequent. However, MS patients and HC displayed the same frequency of autoreactive cells. The epitopes inducing the strongest responses were not those with the highest HLA binding, suggesting an effective thymic selection in MS patients. Our data extend the concept that the frequency of myelin-reactive T cells in MS patient blood is not increased compared to HC. The description of this set of myelin-derived peptides (MHC class I restricted, recognized by CD8+ T cells) offers new tools to explore the CD8+ cell role in MS.
Berthelot
Laureline
L
INSERM U643, et ITERT, Nantes, France.
Laplaud
David-Axel
DA
Pettré
Ségolène
S
Ballet
Caroline
C
Michel
Laure
L
Hillion
Sophie
S
Braudeau
Cécile
C
Connan
Francine
F
Lefrère
Fabienne
F
Wiertlewski
Sandrine
S
Guillet
Jean-Gérard
JG
Brouard
Sophie
S
Choppin
Jeannine
J
Soulillou
Jean-Paul
JP
D000328:Adult; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism; D004676:Myelin Basic Protein / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma