title: Decrypting the spectrum of antigen-specific T-cell responses: the avidity repertoire of MBP-specific T-cells.
abstract: Myelin basic protein (MBP) is a well-characterized autoantigen potentially involved in the pathogenesis of the most common human demyelinating disease of the central nervous system (CNS), multiple sclerosis (MS). It is known that MBP-specific T-cell responses differ widely among different individuals and also within a single donor in terms of fine specificity and functional characteristics including the avidity in antigen recognition. In this report, we demonstrate that the in vitro selection of MBP-reactive T-cell repertoire is strictly dependent upon the antigen dose used in the primary cultures. MBP-specific T-cell lines (TCLs) were generated from MS patients and healthy donors using different antigen concentration in cultures (0.1 to 50 microg/ml). In both MS patients and controls, the number of obtained T-cell lines was affected by the antigen concentration. In addition, low and high antigen concentrations selected in vitro different T-cell populations in terms of peptide specificity patterns and different functional avidities in antigen recognition. Low concentrations of MBP in the primary cultures yielded a small number of TCLs recognizing the specific antigen with higher avidity whereas high antigen concentrations allowed the in vitro expansion of a higher numbers of T-cells recognizing MBP with lower avidity. The use of different antigen concentrations in the primary cultures can be applied as a simple experimental system to investigate the overall avidity repertoire of antigen-specific T-cell response in humans.
authors.affiliation: Department of Neurological and Psychiatric Sciences, University of Florence, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Mazzanti
authors.forename: B
authors.initials: B
authors.lastname: Hemmer
authors.forename: E
authors.initials: E
authors.lastname: Traggiai
authors.forename: C
authors.initials: C
authors.lastname: Ballerini
authors.forename: H F
authors.initials: HF
authors.lastname: McFarland
authors.forename: L
authors.initials: L
authors.lastname: Massacesi
authors.forename: R
authors.initials: R
authors.lastname: Martin
authors.forename: M
authors.initials: M
authors.lastname: Vergelli
mesh_terms: D000915:Antibody Affinity / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000939:Epitopes; D016056:Immunodominant Epitopes; D004676:Myelin Basic Protein