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 individual s and also within a single donor in terms of fine specificity and functiona l characteristics including the avidity in antigen recognition. In this rep ort, we demonstrate that the in vitro selection of MBP-reactive T-cell repe rtoire is strictly dependent upon the antigen dose used in the primary cult ures. MBP-specific T-cell lines (TCLs) were generated from MS patients and healthy donors using different antigen concentration in cultures (0.1 to 50 mu g/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 te rms of peptide specificity patterns and different functional avidities in a ntigen recognition. Low concentrations of MBP in the primary cultures yield ed a small number of TCLs recognizing the specific antigen with higher avid ity whereas high antigen concentrations allowed the in vitro expansion of a higher numbers of T-cells recognizing MBP with lower avidity. The use of d ifferent antigen concentrations in the primary cultures can be applied as a simple experimental system to investigate the overall avidity repertoire o f antigen-specific T-cell response in humans. (C) 2000 Wiley-Liss, Inc.