8536d_ch08_185-199 8/2/02 10:08 AM Page 198 mac79 Mac 79: 45_Bwppldsby et al./ Immunology Se 198 PART II Generation of B-Cell and T-Cell Response ferences 3. L A Morrison and T J. Braciale conducted an experiment to Alfonso, C, and L. Karlsson. 2000. Nonclassical class ii mole determine whether antigens presented by class I or II MHC molecules are processed in different pathways. Their results cules. Ann. Rev. Immunol. 18: 113 are summarized in Table 8-2 Brodsky,EM, et al. 1999. Human pathogen subversion of anti- a. Explain why the class I-restricted Tc cells did not re- en presentation. Immunol. Reviews. 168: 199 spond to target cells infected with UV-inactivated in- Busch, R, et al. 2000. Accessory molecules for MHC class II pep- fluenza virus b. Explain why chloroquine inhibited the response of the class II-restricted Tc cells to live Doherty, P C, and R. M. Zinkernagel. 1975. H-2 compatibility is Explain why emetine inhibited the response of class I- required for T-cell mediated lysis of target cells infected with restricted but not class II-restricted To cells to live Gadola,SD,et al. 2000. TAP deficiency syndrome. Clin. Exp. 4. For each of the following cell components or processes, indi Immunol. 121: 173 cate whether it is involved in t cessing and presentation Ghosh P, M. Amaya, E Mellins, and D. C. Wiley. 1995. The of exogenous antigens(EX), endogenous antigens(EN),or structure of an intermediate in class ll mHc maturation: CLIP both(B). Briefly explain the function of each item. bound to hla-dr3 Nature 378: 457 Class i mhc molecules Jayawardena-Wolf, J, and A Bendelac. 2001. CDI and lipid anti- Class II MHC molecules gens: intracellular pathways for antigen presentation. Curr c Invariant(1i)chains d sosomal hydrolases TAPI and TAP2 proteins Matsuda J L, and M. Kroneberg. 2001. Presentation of self and f microbial lipids by CDI molecules. Curr. Opinion in ImmunoL. Transport of vesicles from the rer to the golgi 13:19. Proteasomes Ortmann, B, et al. 1997. A critical role for tapasin in the assem- h Phagocytosis or end oly and function of multimeric MHC class I-TAP complexes Calnexin Science 277: 1306 CLIP Tapasin Pamer, E, and P. Cresswell. 1998. Mechanisms of MHC class I estricted antigen processing. Annu. Rev. Immunol. 16: 323 5. Antigen-presenting cells have bee Porcelli,S.A, and R L Modlin. 1999. The CDI System: Antigen- lysozyme peptide 46-61 together wit 应 Il IA mole- presenting molecules for T-cell recognition of lipids and gly ule. When CD4 TH cells are incubate PCs and native lysozyme or the synthetic lysozyme 6-61, TH-cell activation occurs Roche, P. A. 1999. Intracellular protein traffic in lymphocytes How do i get there from here? "Immunity 11: 391 a. If chloroquine is added to the incubation mixture, presen- of the native protein is inhibited, but the peptide Van Ham. M. et al. 2000. What to do with HLA-Do? Immuno- continues to induce TH-cell activation. Explain why this genetics 51: 765 occurs Yewdell, J W. 2001. Not such a dismal science: The economics of b. If chloroquine addition is delayed for 3 h, presentation of rotein synthesis, folding, degradation, and antigen process- the native protein is not inhibited. Explain why this occurs ing. Trends in Cell Biol. 11: 294 6. Cells that can present antigen to TH cells have been classified into two groups--professional and nonprof Study Questions a. Name the three types of ional APCs. For each type class II mHc molecules CLINICAL Focus QUESTION Patients with taP deficiency have co-stimulatory signal constitutively or must be activated examples of nonprofessional APCs. When are these cells most likely to function in antigen presentation? erapy treatment for this disease, despite the fact that a single gene defect is implicated 7. Predict whether TH-cell proliferation or CTL-mediated cytol of target cells will occur 1.Explain the difference between the terms antigen-presenting cells. The CD4* TH cells are from lysozyme-primed mice, and cell and target cell, as they the CD8 CTls are from influenza-infected mice. Use r to 2. Define the following terms indicate a response and nR to indicate no response. a. Self-MHC restriction a._H-2 TH cells lysozyme-pulsed H-24 b. Antigen processing C. Endogenous antigen b H-2 TH cells t lysozyme-pulsed H-2 d. Exogenous antigen naclReferences Alfonso, C., and L. Karlsson. 2000. Nonclassical class II mole￾cules. Ann. Rev. Immunol. 18:113. Brodsky, F. M., et al. 1999. Human pathogen subversion of anti￾gen presentation. Immunol. Reviews. 168:199. Busch, R., et al. 2000. Accessory molecules for MHC class II pep￾tide loading. Curr. Opinion in Immunol. 12:99. Doherty, P. C., and R. M. Zinkernagel. 1975. H-2 compatibility is required for T-cell mediated lysis of target cells infected with lymphocytic choriomeningitis virus. J. Exp. Med. 141:502. Gadola, S. D., et al. 2000. TAP deficiency syndrome. Clin. Exp. Immunol. 121:173. Ghosh P., M. Amaya, E. Mellins, and D. C. Wiley. 1995. The structure of an intermediate in class II MHC maturation: CLIP bound to HLA-DR3. Nature 378:457. Jayawardena-Wolf, J., and A. Bendelac. 2001. CD1 and lipid anti￾gens: intracellular pathways for antigen presentation. Curr. Opinions in Immunol. 13:109. Matsuda J. L., and M. Kroneberg. 2001. Presentation of self and microbial lipids by CD1 molecules. Curr. Opinion in Immunol. 13:19. Ortmann, B., et al. 1997. A critical role for tapasin in the assem￾bly and function of multimeric MHC class I–TAP complexes. Science 277:1306. Pamer, E., and P. Cresswell. 1998. Mechanisms of MHC class I– restricted antigen processing. Annu. Rev. Immunol. 16:323. Porcelli, S. A., and R. L. Modlin. 1999. The CD1 System: Antigen￾presenting molecules for T-cell recognition of lipids and gly￾colipids. Ann. Rev. Immunol. 17:297. Roche, P. A. 1999. Intracellular protein traffic in lymphocytes: “How do I get there from here?” Immunity 11:391. Van Ham, M., et al. 2000. What to do with HLA-DO? Immuno￾genetics 51:765. Yewdell, J. W. 2001. Not such a dismal science: The economics of protein synthesis, folding, degradation, and antigen process￾ing. Trends in Cell Biol. 11: 294 Study Questions CLINICAL FOCUS QUESTION Patients with TAP deficiency have partial immunodeficiency as well as autoimmune manifesta￾tions. How do the profiles for patients’ immune cells explain the partial immunodeficiency? Why is it difficult to design a gene therapy treatment for this disease, despite the fact that a single gene defect is implicated? 1. Explain the difference between the terms antigen-presenting cell and target cell, as they are commonly used in immunology. 2. Define the following terms: a. Self-MHC restriction b. Antigen processing c. Endogenous antigen d. Exogenous antigen 3. L. A. Morrison and T. J. Braciale conducted an experiment to determine whether antigens presented by class I or II MHC molecules are processed in different pathways. Their results are summarized in Table 8-2. a. Explain why the class I–restricted TC cells did not re￾spond to target cells infected with UV-inactivated in￾fluenza virus. b. Explain why chloroquine inhibited the response of the class II–restricted TC cells to live virus. c. Explain why emetine inhibited the response of class I– restricted but not class II–restricted TC cells to live virus. 4. For each of the following cell components or processes, indi￾cate whether it is involved in the processing and presentation of exogenous antigens (EX), endogenous antigens (EN), or both (B). Briefly explain the function of each item. a. ______Class I MHC molecules b. ______Class II MHC molecules c. ______Invariant (Ii) chains d. ______Lysosomal hydrolases e. ______TAP1 and TAP2 proteins f. ______Transport of vesicles from the RER to the Golgi complex g. ______Proteasomes h. ______Phagocytosis or endocytosis i. ______Calnexin j. ______CLIP k. ______Tapasin 5. Antigen-presenting cells have been shown to present lysozyme peptide 46–61 together with the class II IAk mole￾cule. When CD4TH cells are incubated with APCs and native lysozyme or the synthetic lysozyme peptide 46–61, TH-cell activation occurs. a. If chloroquine is added to the incubation mixture, presen￾tation of the native protein is inhibited, but the peptide continues to induce TH-cell activation. Explain why this occurs. b. If chloroquine addition is delayed for 3 h, presentation of the native protein is not inhibited. Explain why this occurs. 6. Cells that can present antigen to TH cells have been classified into two groups—professional and nonprofessional APCs. a. Name the three types of professional APCs. For each type indicate whether it expresses class II MHC molecules and a co-stimulatory signal constitutively or must be activated before doing so. b. Give three examples of nonprofessional APCs. When are these cells most likely to function in antigen presentation? 7. Predict whether TH-cell proliferation or CTL-mediated cytol￾ysis of target cells will occur with the following mixtures of cells. The CD4 TH cells are from lysozyme-primed mice, and the CD8 CTLs are from influenza-infected mice. Use R to indicate a response and NR to indicate no response. a. ______H-2k TH cells lysozyme-pulsed H-2k macrophages b. ______H-2k TH cells lysozyme-pulsed H-2b/k macrophages 198 PART II Generation of B-Cell and T-Cell Responses 8536d_ch08_185-199 8/2/02 10:08 AM Page 198 mac79 Mac 79:45_BW:Goldsby et al. / Immunology 5e: