8536d_ch08_185-199 8/2/02 10:08 AM Page 187 mac79 Mac 79: 45_Bwppldsby et al./ Immunology Se Antigen Processing and Presentation CHAPTER 8 187 cell-mediated response could be induced by either the native 8-3a, b). During that interval of 1-3 h, the antigen-presenting or the denatured antigen(see Table 3-5). These findings were cells had processed the antigen and had displayed it on the viewed as an interesting enigma, but implications for antigen membrane in a form able to activate T presentation were completely overlooked until the early Subsequent experiments by R. P. Shimonkevitz showed that internalization and processing could be bypassed if anti- gen-presenting cells were exposed to peptide digests of an Processing of Antigen Is Required antigen instead of the native antigen(Figure 8-3c). In these for Recognition by T Cells experiments, antigen-presenting cells were treated with glu taraldehyde(this chemical, like paraformaldehyde, fixes the The results obtained by K. Ziegler and E. R. Unanue were cell, making the membrane impermeable)and then incu among those that contradicted the prevailing dogma that bated with native ovalbumin or with ovalbumin that had ntigen recognition by B and T cells was basically similar. been subjected to partial enzymatic digestion. The digested These researchers observed that TH-cell activation by bacter- ovalbumin was able to interact with the glutaraldehyde-fixed ial protein antigens was prevented by treating the antigen- antigen-presenting cells, thereby activating ovalbumin presenting cells with paraformaldehyde prior to antigen specific TH cells, whereas the native ovalbumin failed to do posure. However, if the antigen-presenting cells were first so. These results suggest that antigen processing involves the allowed to ingest the antigen and were fixed with paraform- digestion of the protein into peptides that are recognized by ldehyde 1-3 h later, TH-cell activation still occurred( Figure the ovalbumin-specific TH cell EXPERIMENTAL CONDITIONS T-CELL ACTIVA THell APO APC Fixation TH cell APC APC FIGURE8-3Experimental demonstration that antigen process. before antigen exposure and incubated with peptide digests of the ing is necessary for TH-cell activation.(a)When antigen-presenting antigen(rather than native antigen), they also can activate TH cells cells(APCs)are fixed before exposure to antigen, they are unable TH-cell activation is determined by measuring a specific TH-cell to activate TH cells.(b) In contrast, APCs fixed at least 1 h after response(e. g, cytokine secretion antigen exposure can activate TH cells. (c) When APCs are fixedcell-mediated response could be induced by either the native or the denatured antigen (see Table 3-5). These findings were viewed as an interesting enigma, but implications for antigen presentation were completely overlooked until the early 1980s. Processing of Antigen Is Required for Recognition by T Cells The results obtained by K. Ziegler and E. R. Unanue were among those that contradicted the prevailing dogma that antigen recognition by B and T cells was basically similar. These researchers observed that TH-cell activation by bacter￾ial protein antigens was prevented by treating the antigen￾presenting cells with paraformaldehyde prior to antigen exposure. However, if the antigen-presenting cells were first allowed to ingest the antigen and were fixed with paraform￾aldehyde 1–3 h later, TH-cell activation still occurred (Figure 8-3a,b). During that interval of 1–3 h, the antigen-presenting cells had processed the antigen and had displayed it on the membrane in a form able to activate T cells. Subsequent experiments by R. P. Shimonkevitz showed that internalization and processing could be bypassed if anti￾gen-presenting cells were exposed to peptide digests of an antigen instead of the native antigen (Figure 8-3c). In these experiments, antigen-presenting cells were treated with glu￾taraldehyde (this chemical, like paraformaldehyde, fixes the cell, making the membrane impermeable) and then incu￾bated with native ovalbumin or with ovalbumin that had been subjected to partial enzymatic digestion. The digested ovalbumin was able to interact with the glutaraldehyde-fixed antigen-presenting cells, thereby activating ovalbumin￾specific TH cells, whereas the native ovalbumin failed to do so. These results suggest that antigen processing involves the digestion of the protein into peptides that are recognized by the ovalbumin-specific TH cells. Antigen Processing and Presentation CHAPTER 8 187 FIGURE 8-3 Experimental demonstration that antigen process￾ing is necessary for TH-cell activation. (a) When antigen-presenting cells (APCs) are fixed before exposure to antigen, they are unable to activate TH cells. (b) In contrast, APCs fixed at least 1 h after antigen exposure can activate TH cells. (c) When APCs are fixed before antigen exposure and incubated with peptide digests of the antigen (rather than native antigen), they also can activate TH cells. TH-cell activation is determined by measuring a specific TH-cell response (e.g., cytokine secretion). T-CELL ACTIVATION EXPERIMENTAL CONDITIONS + Antigen peptides Fixation APC Fixation – APC APC Antigen 1h Antigen 1h APC APC TH cell APC + Fixation APC TH cell (a) (b) (c) 8536d_ch08_185-199 8/2/02 10:08 AM Page 187 mac79 Mac 79:45_BW:Goldsby et al. / Immunology 5e: