Figure 2.

The possible role of MHC class II stability in the onset of immune-mediated thrombotic thrombocytopenic purpura (iTTP). (A) Intrinsically unstable HLA-DRB1*11 molecules are rapidly endocytosed, thus limiting the exposure of HLA-DRB1*11-loaded peptides on medullary thymic epithelial cells (mTEC) to CD4⁺ T cells. The proposed instability of HLA-DRB1*11/peptide complexes results in inefficient removal of self-reactive CD4⁺ T cells (through induction of apoptosis) in the thymus, and the appearance of potentially self-reactive CD4⁺ T cells in the peripheral lymphoid system.^98,99 (B) Intrinsically stable HLA-DRB1*04 molecules are retained for prolonged periods of time on the surface of mTEC, thereby efficiently eliminating self-reactive CD4⁺ T cells. Consequently, the number of self-reactive CD4⁺ T cells escaping the negative selection in thymus will be very limited, which could account for the protective role of HLA-DRB1*04 in the development of iTTP.