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. 2006 Dec 11;401(Pt 1):121–127. doi: 10.1042/BJ20060847

Figure 3. HLA-A2 is cleaved by PS1/γ-secretase.

Figure 3

(a) Sequence comparison of the APP-ϵ/Notch-S3 domains in ten known human PS1/γ-secretase-like substrates, and in HLA-A2. (b) Predicted fragment sizes before and after PS1/γ-secretase-mediated cleavage of HLA-A2 CTF. (c) CHO cells expressing HLA-A2 were resolved by SDS/12% PAGE and stained with anti-V5. Upon co-treatment with PMA (TPA) and DAPT, an HLA-A2 CTF accumulates around 14 kDa. (d) Anti-V5 immunostaining shows that HLA-A2 CTFs are increased by two additional γ-secretase inhibitor treatments, L-685,458 and WPE31. Transferrin receptor is shown as loading control. (e) Anti-V5 immunostaining of B104 rat neuroblastoma cells stably expressing HLA-A2 shows accumulation of HLA-A2 CTFs after treatment with PMA or DAPT, and further accumulation in co-treatments. Transferrin receptor is shown as loading control. (f) The dominant-negative form of PS1, D385A, elevates HLA-A2 CTF levels. Expression of PS1(D385A) results in the accumulation of the 14 kDa HLA-A2 CTF (arrowhead). The asterisk indicates an unidentified band that is not seen with PS1/γ-secretase inhibitor treatments. (g) Jurkat T-cells show accumulation of an endogenous MHC I CTF. A 24 h incubation of DAPT leads to accumulation of an approx. 12 kDa MHC I CTF. Immunostaining was with anti-HLA-A and -B (TA-17). Transferrin receptor is shown as a control.