TY - JOUR
T1 - The frequency of high avidity T cells determines the hierarchy of determinant spreading
AU - Tian, J.
AU - Gregori, S.
AU - Adorini, L.
AU - Kaufman, D. L.
PY - 2001/6/15
Y1 - 2001/6/15
N2 - Autoimmunity often spreads in a predefined pattern during the progression of T cell-mediated autoimmune diseases. This progression has been well described in animal models and in man, but the basis for this phenomenon is little understood. To gain insight into the factors that determine this spreading hierarchy, we characterized the binding affinity of a panel of β cell-autoantigenic peptides to I-Ag7, as well as the precursor frequency, functional avidity, and phenotype of the T cells that recognize these peptides in type 1 diabetes-prone nonobese diabetic mice. We observed that autoimmunity gradually spreads from a β cell determinant, which had the largest precursor pool of high avidity T cells, to β cell determinants with progressively smaller and lower avidity T cell precursor pools. This correlation between the sequential development of spontaneous T cell autoimmunity and the frequency and avidity of autoantigen-reactive T cells suggests that the extent to which T cells were negatively selected by the self-determinants is the key factor determining the spreading hierarchy.
AB - Autoimmunity often spreads in a predefined pattern during the progression of T cell-mediated autoimmune diseases. This progression has been well described in animal models and in man, but the basis for this phenomenon is little understood. To gain insight into the factors that determine this spreading hierarchy, we characterized the binding affinity of a panel of β cell-autoantigenic peptides to I-Ag7, as well as the precursor frequency, functional avidity, and phenotype of the T cells that recognize these peptides in type 1 diabetes-prone nonobese diabetic mice. We observed that autoimmunity gradually spreads from a β cell determinant, which had the largest precursor pool of high avidity T cells, to β cell determinants with progressively smaller and lower avidity T cell precursor pools. This correlation between the sequential development of spontaneous T cell autoimmunity and the frequency and avidity of autoantigen-reactive T cells suggests that the extent to which T cells were negatively selected by the self-determinants is the key factor determining the spreading hierarchy.
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M3 - Article
C2 - 11390460
AN - SCOPUS:0035876930
VL - 166
SP - 7144
EP - 7150
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -