8536d_ch08_194 8/23/02 11: 59 AM Page 194 mac100 mac 100: 1268_*:8536d: Goldsby et al./Immunology se- 194 PART 11 Generation of B-Cell and T-Cell Response VISUALIZING CONCEPTS Endogenous pathway Exogenous pathway (class I MHC (class II MHC) Endogenous tigen Endogenous antigen is Proteasome Peptid reticulum (RER) RER via TAP Invariant T Class I MHC a and阝 nd invariant chain, TAP blocking binding of endogenous antigen. B2-microglobulin Class I Class ll MHC Calnexin MHC complex is routed Peptide hrough Golgi to Class I MHC o chain binds calnexin, then B2 microglobulin. Calnexin dissociates Calreticulin Golgi complex Invariant chain is and Tapasin bind MHO degraded, leaving CLIF fragment. chaperones dissociate. Digested Invariant④ Exogenous antigen is routed to endocytic pathway compartments Class I MHC-peptide is transported from RER to (③ COe- exogenous Golgi complex to plasma exchange of CLIP for antigenic peptide. Class lI MHC-peptide is Class I Class ll transported to plasma membrane MHC FIGURE 8-8 Separate antigen-presenting pathways are utilized termine whether antigenic peptides associate with class I MHC for endogenous (green )and exogenous(red)antigens. The mode molecules in the rough endoplasmic reticulum or with class ll of antigen entry into cells and the site of antigen processing de- molecules in endocytic compartments protein called invariant chain(li, CD74). This trimeric pro- from binding to the cleft while the class ll molecule is within tein interacts with the peptide-binding cleft of the class il the RER (see right side of Figure 8-8). The invariant chain molecules, preventing any endogenously derived peptides also appears to be involved in the folding of the class ll a and194 PART II Generation of B-Cell and T-Cell Responses VISUALIZING CONCEPTS FIGURE 8-8 Separate antigen-presenting pathways are utilized for endogenous (green) and exogenous (red) antigens. The mode of antigen entry into cells and the site of antigen processing de￾termine whether antigenic peptides associate with class I MHC molecules in the rough endoplasmic reticulum or with class II molecules in endocytic compartments. Endogenous pathway (class I MHC) Exogenous pathway (class II MHC) Peptide TAP Invariant chain Class II MHC Class I MHC Class I MHC Class II MHC Rough endoplasmic reticulum (RER) Proteasome Calreticulum Tapasin β2-microglobulin Golgi complex Digested invariant chain Exogenous antigen CLIP Calnexin Endogenous antigen Class II MHC α and β bind invariant chain, blocking binding of endogenous antigen. 1 Endogenous antigen is degraded by proteasome. 1 Peptide is transported to RER via TAP. 2 MHC complex is routed through Golgi to endocytic pathway compartments. 2 Class I MHC α chain binds calnexin, then β2 microglobulin. Calnexin dissociates, Calreticulin and Tapasin bind. MHC captures peptide, chaperones dissociate. 3 Invariant chain is degraded, leaving CLIP fragment. 3 Exogenous antigen is taken up, degraded, routed to endocytic pathway compartments. Class I MHC–peptide is transported from RER to Golgi complex to plasma membrane. 4 4 HLA-DM mediates exchange of CLIP for antigenic peptide. 5 Class II MHC–peptide is transported to plasma membrane. 6 protein called invariant chain (Ii, CD74). This trimeric pro￾tein interacts with the peptide-binding cleft of the class II molecules, preventing any endogenously derived peptides from binding to the cleft while the class II molecule is within the RER (see right side of Figure 8-8). The invariant chain also appears to be involved in the folding of the class II and 8536d_ch08_194 8/23/02 11:59 AM Page 194 mac100 mac 100: 1268_tm:8536d:Goldsby et al. / Immunology 5e-: