Decrypting the spectrum of antigen-specific T-cell responses: the avidity repertoire of MBP-specific T-cells.
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.
Mazzanti
B
B
Department of Neurological and Psychiatric Sciences, University of Florence, Italy.
Hemmer
B
B
Traggiai
E
E
Ballerini
C
C
McFarland
H F
HF
Massacesi
L
L
Martin
R
R
Vergelli
M
M
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*
D000939:Epitopes; D016056:Immunodominant Epitopes; D004676:Myelin Basic Protein