Human TPP2 deficiency reproduces features of the murine knockout phenotype. (A) Illustration of the single nucleotide deletion at position c.432delG of the TPP2 coding sequence in the index patient (P1) and his asymptomatic sister. (B) Western blot analysis of lysates from Epstein Barr virus (EBV) lines of P1, the healthy heterozygous sister, and a healthy donor (HD) incubated with anti-TPP2 antibodies (upper panel) and anti-actin antibodies as a loading control (lower panel). (C) MHC class I expression on fresh T and B cells of P1 compared with his HLA identical healthy heterozygous sister or 10 adult controls (adult HD). (D) Upregulation of MHC class I expression on control CD4 or CD8 T cells after phytohemagglutinin (PHA) stimulation in the absence (gray) or presence (black) of the TPP2 inhibitor butabindide. (E) β-galactosidase activity of primary fibroblasts isolated from skin biopsies of the patient (P1) or a healthy donor (HD). Experiments (C-E) were performed 3 times with similar results. ABCs, age-associated B cells; Max, maximum; Med, medium; TPPII, tripeptidyl peptidase II.