Achieving stability through editing and chaperoning: Regulation of MHC class II peptide binding and expression

Immunological Reviews

Volumn 207, Issue , 2005, Pages 242-260

  Busch, Robert ^a,b   Rinderknecht, Cornelia H ^a   Roh, Sujin ^a   Lee, Andrew W ^a   Harding, James J ^a   Burster, Timo ^a   Hornell, Tara M C ^a   Mellins, Elizabeth D ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b KINEMED INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HLA DM ANTIGEN; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2;

ANTIGEN BINDING; ANTIGEN EXPRESSION; AUTOIMMUNE DISEASE; AUTOIMMUNE HEPATITIS; CATALYSIS; CELIAC DISEASE; CELL MEMBRANE; DERMATOMYOSITIS; ENDOSOME; ENZYME SPECIFICITY; GOLGI COMPLEX; GRAVES DISEASE; HUMAN; HYDROGEN BOND; IN VITRO STUDY; INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PHENOTYPE; PRIMARY SCLEROSING CHOLANGITIS; PRIORITY JOURNAL; PROTEIN TRANSPORT; REVIEW; RHEUMATOID ARTHRITIS;

ANIMALS; ANTIGEN PRESENTATION; ANTIGENS, DIFFERENTIATION, B-LYMPHOCYTE; AUTOIMMUNITY; HISTOCOMPATIBILITY ANTIGENS CLASS II; HLA-D ANTIGENS; HUMANS; MOLECULAR CHAPERONES; PEPTIDES; PROTEIN BINDING; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN STRUCTURE, QUATERNARY;

EID: 26244444794     PISSN: 01052896     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.0105-2896.2005.00306.x     Document Type: Review

References (148)

1. Busch R, Mellins ED. Developing and shedding inhibitions: how MHC class II molecules reach maturity. Curr Opin Immunol 1996;8:51-58.
2. Busch R, Doebele RC, Patil NS, Pashine A, Mellins ED. Accessory molecules for MHC class II peptide loading. Curr Opin Immunol 2000;12:99-106.
3. Roche PA, Cresswell P. Invariant chain association with HLA-DR molecules inhibits immunogenic peptide binding. Nature 1990;345:615-618.
4. Bakke O, Dobberstein B. MHC class II-associated invariant chain contains a sorting signal for endosomal compartments. Cell 1990;63:707-716.
5. Riberdy JM, Newcomb JR, Surman MJ, Barbosa JA, Cresswell P. HLA-DR molecules from an antigen-processing mutant cell line are associated with invariant chain peptides. Nature 1992;360:474-477.
6. Sloan VS, et al. Mediation by HLA-DM of dissociation of peptides from HLA-DR. Nature 1995;375:802-806.
7. Denzin LK, Cresswell P. HLA-DM induces CUP dissociation from MHC class II alpha beta dimers and facilitates peptide loading. Cell 1995;82:155-165.
8. Weber DA, Evavold BD, Jensen PE. Enhanced dissociation of HLA-DR-bound peptides in the presence of HLA-DM. Science 1996;274:618-620.
9. Kropshofer H, Vogt AB, Moldenhauer G, Hammer J, Blum JS, Hammerling GJ. Editing of the HLA-DR-peptide repertoire by HLA-DM. EMBO J 1996;15:6144-6154.
10. Mellins E, Smith L, Arp B, Cotner T, Celis E, Pious D. Defective processing and presentation of exogenous antigens in mutants with normal HLA class II genes. Nature 1990;343:71-74.
11. Riberdy JM, Cresswell P. The antigen-processing mutant T2 suggests a role for MHC-linked genes in class II antigen presentation. J Immunol 1992;148:2586-2590.
12. Dang LH, Lien LL, Benacerraf B, Rock KL. A mutant antigen-presenting cell defective in antigen presentation expresses class II MHC molecules with an altered conformation. J Immunol 1993;150:4206-4217.
13. Mellins E, Kempin S, Smith L, Monji T, Pious D. A gene required for class II-restricted antigen presentation maps to the major histocompatibility complex. J Exp Med 1991;174:1607-1615.
14. Morris P, et al. An essential role for HLA-DM in antigen presentation by class II major histocompatibility molecules. Nature 1994;368:551-554.
15. Fling SP, Arp B, Pious D. HLA-DMA and -DMB genes are both required for MHC class II/peptide complex formation in antigen-presenting cells. Nature 1994;368:554-558.
16. Denzin LK, Robbins NF, Carboy-Newcomb C, Cresswell P. Assembly and intracellular transport of HLA-DM and correction of the class II antigen-processing defect in T2 cells. Immunity 1994;1:595-606.
17. Mellins E, et al. A mutant human histocom-patibility leukocyte antigen DR molecule associated with invariant chain peptides. J Exp Med 1994;179:541-549.
18. Sette A, et al. Invariant chain peptides in most HLA-DR molecules of an antigen-processing mutant. Science 1992;258:1801-1804.
19. Vogt AB, Kropshofer H, Moldenhauer G, Hammerling GJ. Kinetic analysis of peptide loading onto HLA-DR molecules mediated by HLA-DM. Proc Natl Acad Sci USA 1996;93:9724-9729.
20. Kelly AP, Monaco JJ, Cho SG, Trowsdale J. A new human HLA class II-related locus, DM. Nature 1991;353:571-573.
21. Shaman J, von Scheven E, Morris P, Chang MD, Mellins E. Analysis of HLA-DMB mutants and -DMB genomic structure. Immunogenetics 1995;41:117-124.
22. Busch R, Doebele RC, von Scheven E, Fahrni J, Mellins ED. Aberrant intermolecular disulfide bonding in a mutant HLA-DM molecule: implications for assembly, maturation, and function. J Immunol 1998;160:734-743.
23. Busch R, Reich Z, Zaller DM, Sloan V, Mellins ED. Secondary structure composition and pH-dependent conformational changes of soluble recombinant HLA-DM. J Biol Chem 1998;273:27557-27564.
24. Mosyak L, Zaller DM, Wiley DC. The structure of HLA-DM, the peptide exchange catalyst that loads antigen onto class II MHC molecules during antigen presentation. Immunity 1998;9:377-383.
25. Fremont DH, Crawford F, Marrack P, Hendrickson WA, Kappler J. Crystal structure of mouse H2-M. Immunity 1998;9:385-393.
26. Doebele RC, Busch R, Scott HM, Pashine A, Mellins ED. Determination of the HLA-DM interaction site on HLA-DR molecules. Immunity 2000;13:517-527.
27. Denzin LK, Hammond C, Cresswell P. HLA-DM interactions with intermediates in HLA-DR maturation and a role for HLA-DM in stabilizing empty HLA-DR molecules. J Exp Med 1996;184:2153-2165.
28. Weber DA, Dao CT, Jun J, Wigal JL, Jensen PE. Transmembrane domain-mediated colocalization of HLA-DM and HLA-DR is required for optimal HLA-DM catalytic activity. J Immunol 2001;167:5167-5174.
29. Busch R, Pashine A, Garcia KC, Mellins ED. Stabilization of soluble, low-affinity HLA-DM/HLA-DR1 complexes by leucine zippers. J Immunol Methods 2002;263:111-121.
30. Pashine A, et al. Interaction of HLA-DR with an acidic face of HLA-DM disrupts sequence-dependent interactions with peptides. Immunity 2003;19:183-192.
31. Faubert A, Samaan A, Thibodeau J. Functional analysis of tryptophans alpha 62 and beta 120 on HLA-DM. J Biol Chem 2002;277:2750-2755.
32. Doebele RC, et al. Point mutations in or near the antigen-binding groove of HLA-DR3 implicate class II-associated invariant chain peptide affinity as a constraint on MHC class II polymorphism. J Immunol 2003;170:4683-4692.
33. Chou CL, Sadegh-Nasseri S. HLA-DM recognizes the flexible conformation of major histocompatibility complex class II. J Exp Med 2000;192:1697-1706.
34. Stratikos E, Wiley DC, Stern LJ. Enhanced catalytic action of HLA-DM on the exchange of peptides lacking backbone hydrogen bonds between their N-terminal region and the MHC class II alpha-chain. J Immunol 2004;172:1109-1117.
35. Stratikos E, Mosyak L, Zaller DM, Wiley DC. Identification of the lateral interaction surfaces of human histocompatibility leukocyte antigen (HIA)-DM with HLA-DR1 by formation of tethered complexes that present enhanced HLA-DM catalysis. J Exp Med 2002;196:173-183.
36. van Ham SM, Gruneberg U, Malcherek G, Broker I, Melms A, Trowsdale J. Human histocompatibility leukocyte antigen (HLA)-DM edits peptides presented by HLA-DR according to their ligand binding motifs. J Exp Med 1996;184:2019-2024.
37. McFarland BJ, Beeson C. Binding interactions between peptides and proteins of the class II major histocompatibility complex. Med Res Rev 2002;22:168-203.
38. Siklodi B, et al. Binding affinity independent contribution of peptide length to the stability of peptide-HLA-DR complexes in live antigen presenting cells. Hum Immunol 1998;59:463-471.
39. Raddrizzani L, et al. Identification of destabilizing residues in HLA class II-selected bacteriophage display libraries edited by HLA-DM. Eur J Immunol 1999;29:660-668.
40. Falk K, et al. Ligand exchange of major histocompatibility complex class II proteins is triggered by H-bond donor groups of small molecules. J Biol Chem 2002;277:2709-2715.
41. Marin-Esteban V, Falk K, Rotzschke O. 'Chemical analogues' of HLA-DM can induce a peptide-receptive state in HLA-DR molecules. J Biol Chem 2004;279:50684-50690.
42. McFarland BJ, Katz JF, Beeson C, Sant AJ. Energetic asymmetry among hydrogen bonds in MHC class II*peptide complexes. Proc Natl Acad Sci USA 2001;98:9231-9236.
43. McFarland BJ, Beeson C, Sant AJ. Cutting edge: a single, essential hydrogen bond controls the stability of peptide-MHC class II complexes. J Immunol 1999;163:3S67-3S71.
44. Jardetzky TS, Gorga JC, Busch R, Rodibard J, Strominger JL, Wiley DC. Peptide binding to HLA-DR1: a peptide with most residues substituted to alanine retains MHC binding. EMBO J 1990;9:1797-1803.
45. Belmares MP, Busch R, Wucherpfennig KW, McConnell HM, Mellins ED. Structural factors contributing to DM susceptibility of MHC class II/peptide complexes. J Immunol 2002;169:5109-5117.
46. Katz JF, Stebbins C, Appella E, Sant AJ. Invariant chain and DM edit self-peptide presentation by major histocompatibility complex (MHC) class II molecules. J Exp Med 1996;184:1747-1753.
47. Belmares MP, Busch R, Mellins ED, McConnell HM. Formation of two peptide/MHC II isomers is catalyzed differentially by HLA-DM. Biochemistry 2003;42:838-847.
48. Guerra CB, et al. Novel glycosylation of HLA-DRalpha disrupts antigen presentation without altering endosomal localization. J Immunol 1998;160:4289-4297.
49. Schafer PH, Green JM, Malapati S, Gu L, Pierce SK. HLA-DM is present in one-fifth the amount of HLA-DR in the class II peptide-loading compartment where it associates with leupeptin-induced peptide (LIP)-HLA-DR complexes. J Immunol 1996;157:5487-5495.
50. Chen X, et al. Regulated expression of human histocompatibility leukocyte antigen (HLA) -DO during antigen-dependent and antigen-independent phases of B cell development. J Exp Med 2002;195:1053-1062.
51. Chicz RM, et al. Predominant naturally processed peptides bound to HLA-DR1 are derived from MHC-related molecules and are heterogeneous in size. Nature 1992;358:764-768.
52. Buus S, Sette A, Colon SM, Grey HM. Autologous peptides constitutively occupy the antigen binding site on Ia. Science 1988;242:1045-1047.
53. Frayser M, Sato AK, Xu L, Stern LJ. Empty and peptide-loaded class II major histocompatibility complex proteins produced by expression in Escherichia coli and folding in vitro. Protein Expr Purif 1999;15:105-114.
54. Altman JD, Reay PA, Davis MM. Formation of functional peptide complexes of class II major histocompatibility complex proteins from subunits produced in Escherichia coli. Proc Nad Acad Sci USA 1993;90:10330-10334.
55. Joshi RV, Zarutskie JA, Stern LJ. A three-step kinetic mechanism for peptide binding to MHC class II proteins. Biochemistry 2000;39:3751-3762.
56. Zarutskie JA, Busch R, Zavala-Ruiz Z, Rushe M, Mellins ED, Stern LJ. The kinetic basis of peptide exchange catalysis by HLA-DM. Proc Natl Acad Sci USA 2001;98:12450-12455.
57. Kropshofer H, Arndt SO, Moldenhauer G, Hammerling GJ, Vogt AB. HLA-DM acts as a molecular chaperone and rescues empty HLA-DR molecules at lysosomal pH. Immunity 1997;6:293-302.
58. Rabinowitz JD, et al. Formation of a highly peptide-receptive state of class II MHC. Immunity 1998;9:699-709.
59. Kasson PM, Rabinowitz JD, Schmitt L, Davis MM, McConnell HM. Kinetics of peptide binding to the class II MHC protein I-Ek. Biochemistry 2000;39:1048-1058.
60. Natarajan SK, Stern LJ, Sadegh-Nasseri S. Sodium dodecyl sulfate stability of HLA-DR1 complexes correlates with burial of hydrophobic residues in pocket 1. J Immunol 1999;162:3463-3470.
61. Bankovich AJ, Girvin AT, Moesta AK, Garcia KC. Peptide register shifting within the MHC groove: theory becomes reality. Mol Immunol 2004;40:1033-1039.
62. Belmares MP, McConnell HM. Kinetics of registry selection of chimeric peptides binding to MHC II. Biochemistry 2001;40:10284-10292.
63. Nanda NK, Sant AJ. DM determines the cryptic and immunodominant fate of T cell epitopes. J Exp Med 2000;192:781-788.
64. Hall FC, et al. Relationship between kinetic stability and immunogenicity of HLA-DR4/peptide complexes. Eur J Immunol 2002;32:662-670.
65. Anderson KS, Cresswell P. A role for calnexin (IP90) in the assembly of class II MHC molecules. EMBO J 1994;13:675-682.
66. Lotteau V, et al. Intracellular transport of class II MHC molecules directed by invariant chain. Nature 1990;348:600-605.
67. Ghosh P, Amaya M, Mellins E, Wiley DC. The structure of an intermediate in class II MHC maturation: CUP bound to HLA-DR3. Nature 1995;378:457-462.
68. Zhong G, Castellino F, Romagnoli P, Germain RN. Evidence that binding site occupancy is necessary and sufficient for effective major histocompatibility complex (MHC) class II transport through the secretory pathway redefines the primary function of class II-associated invariant chain peptides (CLIP). J Exp Med 1996;184:2061-2066.
69. Bonnerot C, et al. Association with BiP and aggregation of class II MHC molecules synthesized in the absence of invariant chain. EMBO J 1994;13:934-944.
70. Busch R, Cloutier I, Sekaly RP, Hammerling GJ. Invariant chain protects class II histocompatibility antigens from binding intact polypeptides in the endoplasmic reticulum. EMBO J 1996;15:418-428.
71. Viville S, et al. Mice lacking the MHC class II-associated invariant chain. Cell 1993;72:635-648.
72. Elliott EA, et al. The invariant chain is required for intracellular transport and function of major histocompatibility complex class II molecules. J Exp Med 1994;179:681-694.
73. + T cell selection in mice lacking invariant chain expression. J Exp Med 1993;177:1699-1712.
74. + T cells in the periphery and secondary proliferative responses elicited upon peptide challenge. J Immunol 1999;163:232-241.
75. Rovere P, Forquet F, Zimmermann VS, Trucy J, Ricciardi-Castagnoli P, Davoust J. Dendritic cells from mice lacking the invariant chain express high levels of membrane MHC class II molecules in vivo. Adv Exp Med Biol 1997;417:195-201.
76. Rajagopalan G, Smart MK, Krco CJ, David CS. Expression and function of transgenic HLA-DQ molecules and lymphocyte development in mice lacking invariant chain. J Immunol 2002;169:1774-1783.
77. Sette A, Southwood S, Miller J, Appella E. Binding of major histocompatibility complex class II to the invariant chain-derived peptide, CLIP, is regulated by allelic polymorphism in class II. J Exp Med 1995;181:677-683.
78. Liang MN, Beeson C, Mason K, McConnell HM. Kinetics of the reactions between the invariant chain (85-99) peptide and proteins of the murine class II MHC. Int Immunol 1995;7:1397-1404.
79. Patil NS, et al. Rheumatoid arthritis (RA)-associated HLA-DR alleles form less stable complexes with class II-associated invariant chain peptide than non-RA-associated HLA-DR alleles. J Immunol 2001;167:7157-7168.
80. Miyazaki T, et al. Mice lacking H2-M complexes, enigmatic elements of the MHC class II peptide-loading pathway. Cell 1996;84:531-541.
81. Hedley ML, Urban RG, Strominger JL. Assembly and peptide binding of major histocompatibility complex class II heterodimers in an in vitro translation system. Proc Natl Acad Sci USA 1994;91:10479-10483.
82. Reed AM, Collins EJ, Shock LP, Klapper DG, Frelinger JA. Diminished class II-associated Ii peptide binding to the juvenile dermatomyositis HLA-DQ alpha 1 *0501/DQ beta 1 *0301 molecule. J Immunol 1997;159:6260-6265.
83. Honey K, Forbush K, Jensen PE, Rudensky AY. Effect of decreasing the affinity of the class II-associated invariant chain peptide on the MHC class II peptide repertoire in the presence or absence of H-2M. J Immunol 2004;172:4142-4150.
84. Park SJ, Sadegh-Nasseri S, Wiley DC. Invariant chain made in Escherichia coli has an exposed N-terminal segment that blocks antigen binding to HLA-DR1 and a trimeric C-terminal segment that binds empty HLA-DR1. Proc Natl Acad Sci USA 1995;92:11289-11293.
85. Thayer WP, Ignatowicz L, Weber DA, Jensen PE. Class II-associated invariant chain peptide-independent binding of invariant chain to class II MHC molecules. J Immunol 1999;162:1502-1509.
86. Vogt AB, Stern LJ, Amshoff C, Dobberstein B, Hammerling GJ, Kropshofer H. Interference of distinct invariant chain regions with superantigen contact area and antigenic peptide binding groove of HLA-DR. J Immunol 1995;155:4757-4765.
87. Castellino F, Han R, Germain RN. The transmembrane segment of invariant chain mediates binding to MHC class II molecules in a CLIP-independent manner. Eur J Immunol 2001;31:841-850.
88. Pierre P, Shachar I, Matza D, Gatti E, Flavell RA, Mellman I. Invariant chain controls H2-M proteolysis in mouse splenocytes and dendritic cells. J Exp Med 2000;191:1057-1062.
89. Martin WD, Hicks GG, Mendiratta SK, Leva HI, Ruley HE, Van Kaer L. H2-M mutant mice are defective in the peptide loading of class II molecules, antigen presentation, and T cell repertoire selection. Cell 1996;84:543-550.
90. Fung-Leung WP, et al. Antigen presentation and T cell development in H2-M-deficient mice. Science 1996;271:1278-12781.
91. Gautam AM, et al. Identification of residues in the class II-associated Ii peptide (CLIP) region of invariant chain that affect efficiency of MHC class II-mediated antigen presentation in an allele-dependent manner. J Immunol 1997;159:2782-2788.
92. Zechel MA, Chaturvedi P, Lee-Chan EC, Rider BJ, Singh B. Modulation of antigen presentation and class II expression by a class II-associated invariant chain peptide. J Immunol 1996;156:4232-4239.
93. Lightstone L, et al. In the absence of the invariant chain, HLA-DR molecules display a distinct array of peptides which is influenced by the presence or absence of HLA-DM. Proc Natl Acad Sci USA 1997;94:5772-5777.
94. Lieh JD, Jayne JA, Zhou D, Elliott JF, Blum JS. Editing of an immunodominant epitope of glutamate decarboxylase by HLA-DM. J Immunol 2003;171:853-859.
95. Stang E, Guerra CB, Amaya M, Paterson Y, Bakke O, Mellins ED. DR/CLIP (class II-associated invariant chain peptides) and DR/peptide complexes colocalize in prelysosomes in human B lymphoblastoid cells. J Immunol 1998;160:4696-4707.
96. Eastman S, et al. A study of complexes of class II invariant chain peptide: major histocompatibility complex class II molecules using a new complex-specific monoclonal antibody. Eur J Immunol 1996;26:385-393.
97. + T cell maturation in BALB/c mice. J Immunol 2001;166:5087-5098.
98. Koonce CH, Wutz G, Robertson EJ, Vogt AB, Kropshofer H, Bikoff EK. DM loss in k haplotype mice reveals isotype-specific chaperone requirements. J Immunol 2003;170:3751-3761.
99. Wolf PR, Tourne S, Miyazaki T, Benoist C, Mathis D, Ploegh HL. The phenotype of H-2M-deficient mice is dependent on the MHC class II molecules expressed. Eur J Immunol 1998;28:2605-2618.
100. Drover S, Kovats S, Masewicz S, Blum JS, Nepom GT. Modulation of peptide-dependent allospecific epitopes on HLA-DR4 molecules by HLA-DM. Hum Immunol 1998;59:77-86.
101. Verreck FA, Fargeas CA, Hammerling GJ. Conformational alterations during biosynthesis of HLA-DR3 molecules controlled by invariant chain and HLA-DM. Eur J Immunol 2001;31:1029-1036.
102. Pu Z, Lovitch SB, Bikoff EK, Unanue ER. T cells distinguish mhc-peptide complexes formed in separate vesicles and edited by H2-DM. Immunity 2004;20:467-476.
103. Rajagopalan G, Smart MK, Cheng S, Krco CJ, Johnson KL, David CS. Expression and function of HLA-DR3 and DQ8 in transgenic mice lacking functional H2-M. Tissue Antigens 2003;62:149-161.
104. Fallas JL, Tobin HM, Lou O, Guo D, Sant'Angelo DB, Denzin LK. Ectopic expression of HLA-DO in mouse dendritic cells diminishes MHC class II antigen presentation. J Immunol 2004;173:1549-1560.
105. Nelson CA, Petzold SJ, Unanue ER. Peptides determine the lifespan of MHC class II molecules in the antigen-presenting cell. Nature 1994;371:250-252.
106. Lanzavecchia A, Reid PA, Watts C. Irreversible association of peptides with class II MHC molecules in living cells. Nature 1992;357:249-252.
107. Busch R, Momburg F, Hammerling GJ. Cell surface induction of MHC class II proteins by peptide ligands. Immunobiology 1991;183:267-268.
108. Germain RN, Rinker AG Jr. Peptide binding inhibits protein aggregation of invariant-chain free class II dimers and promotes surface expression of occupied molecules. Nature 1993;363:725-728.
109. Carven GJ, et al. Monoclonal antibodies specific for the empty conformation of HLA-DR1 reveal aspects of the conformational change associated with peptide binding. J Biol Chem 2004;279:16561-16570.
110. Reich Z, et al. Stability of empty and peptide-loaded class II major histocompatibility complex molecules at neutral and endosomal pH: comparison to class I proteins. Proc Natl Acad Sci USA 1997;94:2495-2500.
111. Pinet V, Vergelli M, Martin R, Bakke O, Long EO. Antigen presentation mediated by recycling of surface HLA-DR molecules. Nature 1995;375:603-606.
112. Sekaly RP, Jacobson S, Richert JR, Tonnelle C, McFarland HF, Long EO. Antigen presentation to HLA class II-restricted measles virus-specific T-cell clones can occur in the absence of die invariant chain. Proc Natl Acad Sci USA 1988;85:1209-1212.
113. Poloso NJ, Muntasell A, Roche PA. MHC class II molecules traffic into lipid rafts during intracellular transport. J Immunol 2004;173:4539-4546.
114. Kropshofer H, et al. Tetraspan microdomains distinct from lipid rafts enrich select peptide-MHC class II complexes. Nat Immunol 2002;3:61-68.
115. Anderson HA, Hiltbold EM, Roche PA. Concentration of MHC class II molecules in lipid rafts facilitates antigen presentation. Nat Immunol 2000;1:156-162.
116. Rohn TA, et al. Upregulation of the CLIP self peptide on mature dendritic cells antagonizes T helper type 1 polarization. Nat Immunol 2004;5:909-918.
117. Hiltbold EM, Poloso NJ, Roche PA. MHC class II-peptide complexes and APC lipid rafts accumulate at the immunological synapse. J Immunol 2003;170:1329-1338.
118. Hess AD, Bright EC, Thoburn C, Vogelsang GB, Jones RJ, Kennedy MJ. Specificity of effector T lymphocytes in autologous graft-versus-host disease: role of die major histocompatibility complex class II invariant chain peptide. Blood 1997;89:2203-2209.
119. Kouskoff V, Korganow AS, Duchatelle V, Degott C, Benoist C, Mathis D. Organ-specific disease provoked by systemic autoim-munity. CeU 1996;87:811-822.
120. Picca CC, Caton AJ. The role of self-peptides in the development of CD4+CD25+ regulatory T cells. Curr Opin Immunol 2005;17:131-136.
121. Brown DR, Swier K, Moskowitz NH, Naujokas MF, Locksley RM, Reiner SL. T helper subset differentiation in die absence of invariant chain. J Exp Med 1997;185:31-41.
122. Chaturvedi P, Hengeveld R, Zechel MA, Lee-Chan E, Singh B. The functional role of class II-associated invariant chain peptide (CLIP) in its ability to variably modulate immune responses. Int Immunol 2000;12:757-765.
123. Farr A, DeRoos PC, Eastman S, Rudensky AY. Differential expression of CUP. MHC class II and conventional endogenous peptide: MHC class II complexes by thymic epithelial cells and peripheral antigen-presenting cells. Eur J Immunol 1996;26:3185-3193.
124. Ridgway WM, Fasso M, Fathman CG. A new look at MHC and autoimmune disease. Science 1999;284:749-751.
125. Nepom GT, Kwok WW. Molecular basis for HLA-DQ associations with IDDM. Diabetes 1998;47:1177-1184.
126. Ng AW, Bidani A, Heming TA. Innate host defense of the lung: effects of lung-lining fluid pH. Lung 2004;182:297-317.
127. Radu CG, Nijagal A, McLaughlin J, Wang L, Witte ON. Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells. Proc Natl Acad Sci USA 2005;102:1632-1637.
128. Louis-Plence P, et al. The down-regulation of HLA-DM gene expression in rheumatoid arthritis is not related to their promoter polymorphism. J Immunol 2000;165:4861-4869.
129. Slavin AJ, et al. Requirement for endocytic antigen processing and influence of invariant chain and H-, 2M deficiencies in CNS autoimmunity. J Clin Invest 2001;108:1133-1139.
130. Tompkins SM, Padilla J, Dal Canto MC, Ting JP, Van Kaer L, Miller SD. De novo central nervous system processing of myelin antigen is required for the initiation of experimental autoimmune encephalomyelitis. J Immunol 2002;168:4173-4183.
131. Wubbolts R, et al. Direct vesicular transport of MHC class II molecules from lysosomal structures to the cell surface. J Cell Biol 1996;135:611-622.
132. Raposo G, et al. B lymphocytes secrete antigen-presenting vesicles. J Exp Med 1996;183:1161-1172.
133. Boes M, Cuvillier A, Ploegh H. Membrane specializations and endosome maturation in dendritic cells and B cells. Trends Cell Biol 2004;14:175-183.
134. Sallusto F, Lanzavecchia A. Mobilizing dendritic cells for tolerance, priming, and chronic inflammation. J Exp Med 1999;189:611-614.
135. Villadangos JA, et al. MHC class II expression is regulated in dendritic cells inde-pendently of invariant chain degradation. Immunity 2001;14:739-749.
136. Kleijmeer M, et al. Reorganization of multivesicular bodies regulates MHC class II antigen presentation by dendritic cells. J Cell Biol 2001;155:53-63.
137. Koppelman B, Neefjes JJ, de Vries JE, de Waal Malefyt R. Interleukin-10 down-regulates MHC class II alphabeta peptide complexes at the plasma membrane of monocytes by affecting arrival and recycling. Immunity 1997;7:861-871.
138. Odeberg J, et al. The human cytomegalo-virus protein UL16 mediates increased resistance to natural killer cell cytotoxicity through resistance to cytolytic proteins. J Virol 2003:77:4539-4545.
139. Shumilla JA, et al. Bordetella pertussis infection of primary human monocytes alters HLA-DR expression. Infect Immun 2004;72:1450-1462.
140. Mitchell EK, Mastroeni P, Kelly AP, Trowsdale J. Inhibition of cell surface MHC class II expression by Salmonella. Eur J Immunol 2004;34:2559-2567.
141. Chow A, Toomre D, Garrett W, Mellman I. Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane. Nature 2002;418:988-994.
142. Boes M, et al. T-cell engagement of dendritic cells rapidly rearranges MHC class II transport. Nature 2002;418:983-988.
143. Strettell MD, et al. Allelic basis for HLA-encoded susceptibility to type 1 autoimmune hepatitis. Gastroenterology 1997;112:2028-2035.
144. Cotner T, Schleitz D, Yates JR III. DM-independent release of CLIP peptide from DRB3 isotype DRw52*0101. FASEB J 2000;14:151.15.
145. Hu R, Beck C, Chang YB, DeGroot LJ. HLA class II genes in Graves' disease. Autoimmunity 1992;12:103-106.
146. Hausmann DH, Yu B, Hausmann S, Wucherpfennig KW. pH-dependent peptide binding properties of the type I diabetes-associated I-Ag7 molecule: rapid release of CLIP at an endosomal pH. J Exp Med 1999;189:1723-1734.
147. Buckner J, Kwok WW, Nepom B, Nepom GT. Modulation of HLA-DQ binding properties by differences in class II dimer stability and pH-dependent peptide interactions. J Immunol 1996;157:4940-4945.
148. Vartdal F, et al. The peptide binding motif of the disease associated HLA-DQ (alpha 1 *0501, beta 1 *0201) molecule. Eur J Immunol 1996;26:2764-2772.