8536d_ch08_185-199 8/2/02 10: 08 AM Page 189 mac79 Mac 79: 45_BWfpldsby et al./ Immunology 5e Antigen Processing and Presentation CHAPTER 8 189 CYTOSOLIC PATHWAY Endogcnous-ATP-Cytoplasmic--Peptides TAP Endoplasmic--Peptide-cassI proteasome reticulum MHC complex Exopeptidases、 Amino acids ENDOCYTIC PATHWAY Exogen Endocytic compartments Endow phagocytosis FIGURE 8-4 Overview of cytosolic and endocytic pathways for to the cell membrane. TAP(transporter of antigenic peptides) processing antigen. The proteasome complex contains enzymes transports the peptides to the endoplasmic reticulum. It should be that cleave peptide bonds, converting proteins into peptides. The noted that the ultimate fate of most peptides in the cell is neither antigenic peptides from proteasome cleavage and those from of these pathways, but rather to be degraded completely into endocytic compartments associate with class I or class ll MHc amino acids molecules, and the peptide- MHC complexes are then transported others as well, the association of T-cell function with MHc only to target cells treated with infectious virions. Similarly, restriction is not absolute). In one set of experiments, target target cells that had been treated with infectious influenza cells that expressed both class I and class lI MHC molecules irions in the presence of emetine, which inhibits viral pro were incubated with infectious influenza virus or with UV- tein synthesis, stimulated the class II-restricted Tc cells but inactivated influenza virus. (The inactivated virus retained not the class I-restricted Tc cells. Conversely, target cells that its antigenic properties but was no longer capable of replicat- had been treated with infectious virions in the presence of ing within the target cells. ) The target cells were then incu- chloroquine, a drug that blocks the endocytic processing bated with the class I-restricted or the atypical class II- pathway, stimulated class I- but not class II-restricted Tc restricted Tc cells and subsequent lysis of the target cells was cells determined. The results of their experiments, presented in These results support the distinction between the process- Table 8-2, show that the class Il-restricted Tc cells responded ing of exogenous and endogenous antigens, including the to target cells treated with either infectious or noninfectious preferential association of exogenous antigens with class Il influenza virions. The class I-restricted Tc cells responded MHC molecules and of endogenous antigens with class I TABLE Effect of antigen presentation on activation of class I and class ll MHC-restricted Tc cells CTL ACTIVITYt Class I restricted Class il restricte UV-inactivated virus(noninfectious) Infectious virus chloroquine Target cells, which expressed both class I and class ll MHC molecules, were treated with the indicated preparations of influenza virus and other agents. Emetine inhibits viral protein synthesis, and chloroquine inhibits the endocytic processing pathway. DEtermined by lysis(+)and no lysis(-)of the target cells. SOURCE: Adapted from T. ). Braciale et al, 1987, Immunol. Rev. 98: 95others as well, the association of T-cell function with MHC restriction is not absolute). In one set of experiments, target cells that expressed both class I and class II MHC molecules were incubated with infectious influenza virus or with UV￾inactivated influenza virus. (The inactivated virus retained its antigenic properties but was no longer capable of replicat￾ing within the target cells.) The target cells were then incu￾bated with the class I–restricted or the atypical class II– restricted TC cells and subsequent lysis of the target cells was determined. The results of their experiments, presented in Table 8-2, show that the class II–restricted TC cells responded to target cells treated with either infectious or noninfectious influenza virions. The class I–restricted TC cells responded only to target cells treated with infectious virions. Similarly, target cells that had been treated with infectious influenza virions in the presence of emetine, which inhibits viral pro￾tein synthesis, stimulated the class II–restricted TC cells but not the class I–restricted TC cells. Conversely, target cells that had been treated with infectious virions in the presence of chloroquine, a drug that blocks the endocytic processing pathway, stimulated class I– but not class II–restricted TC cells. These results support the distinction between the process￾ing of exogenous and endogenous antigens, including the preferential association of exogenous antigens with class II MHC molecules and of endogenous antigens with class I Antigen Processing and Presentation CHAPTER 8 189 FIGURE 8-4 Overview of cytosolic and endocytic pathways for processing antigen. The proteasome complex contains enzymes that cleave peptide bonds, converting proteins into peptides. The antigenic peptides from proteasome cleavage and those from endocytic compartments associate with class I or class II MHC molecules, and the peptide-MHC complexes are then transported to the cell membrane. TAP (transporter of antigenic peptides) transports the peptides to the endoplasmic reticulum. It should be noted that the ultimate fate of most peptides in the cell is neither of these pathways, but rather to be degraded completely into amino acids. CYTOSOLIC PATHWAY ENDOCYTIC PATHWAY Endogenous antigens ± Ubiquitin ATP Exogenous antigens Cytoplasmic proteasome complex Peptides Peptides TAP Endoplasmic reticulum Peptide–class I MHC complex Peptide–class II MHC complex Exopeptidases Amino acids Endocytosis or phagocytosis Endocytic compartments TABLE 8-2 Effect of antigen presentation on activation of class I and class II MHC-restricted TC cells CTL ACTIVITY† Treatment of target cells* Class I restricted Class II restricted Infectious virus UV-inactivated virus (noninfectious)  Infectious virus emetine  Infectious virus chloroquine  * Target cells, which expressed both class I and class II MHC molecules, were treated with the indicated preparations of influenza virus and other agents. Emetine inhibits viral protein synthesis, and chloroquine inhibits the endocytic processing pathway. † Determined by lysis () and no lysis () of the target cells. SOURCE: Adapted from T. J. Braciale et al., 1987, Immunol. Rev. 98:95. 8536d_ch08_185-199 8/2/02 10:08 AM Page 189 mac79 Mac 79:45_BW:Goldsby et al. / Immunology 5e: