Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1995 Dec 2;131(6):1403–1419. doi: 10.1083/jcb.131.6.1403

Misfolded major histocompatibility complex class I molecules accumulate in an expanded ER-Golgi intermediate compartment

PMCID: PMC2120650  PMID: 8522600

Abstract

Misfolded membrane proteins are rapidly degraded, often shortly after their synthesis and insertion in the endoplasmic reticulum (ER), but the exact location and mechanisms of breakdown remain unclear. We have exploited the requirement of MHC class I molecules for peptide to achieve their correct conformation: peptide can be withheld by introducing a null mutation for the MHC-encoded peptide transporter, TAP. By withholding TAP-dependent peptides, the vast majority of newly synthesized class I molecules fails to leave the endoplasmic reticulum and is degraded. We used mice transgenic for HLA-B27 on a TAP1- deficient background to allow visualization by immunoelectron microscopy of misfolded HLA-B27 molecules in thymic epithelial cells. In such HLA transgenic animals, the TAP mutation can be considered a genetic switch that allows control over the extent of folding of the protein of interest, HLA-B27, while the rate of synthesis of the constituent subunits remains unaltered. In TAP1-deficient, HLA-B27 transgenic animals, HLA-B27 molecules fail to assemble correctly, and do not undergo carbohydrate modifications associated with the Golgi apparatus, such as conversion to Endoglycosidase H resistance, and acquisition of sialic acids. We show that such molecules accumulate in an expanded network of tubular and fenestrated membranes. This compartment has its counterpart in normal thymic epithelial cells, and is identified as an ER-Golgi intermediate. We detect the presence of ubiquitin and ubiquitin-conjugating enzymes in association with this compartment, suggesting a nonlysosomal mode of degradation of its contents.

Full Text

The Full Text of this article is available as a PDF (7.2 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander J., Payne J. A., Murray R., Frelinger J. A., Cresswell P. Differential transport requirements of HLA and H-2 class I glycoproteins. Immunogenetics. 1989;29(6):380–388. doi: 10.1007/BF00375866. [DOI] [PubMed] [Google Scholar]
  2. Amara J. F., Lederkremer G., Lodish H. F. Intracellular degradation of unassembled asialoglycoprotein receptor subunits: a pre-Golgi, nonlysosomal endoproteolytic cleavage. J Cell Biol. 1989 Dec;109(6 Pt 2):3315–3324. doi: 10.1083/jcb.109.6.3315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Anderson K. S., Alexander J., Wei M., Cresswell P. Intracellular transport of class I MHC molecules in antigen processing mutant cell lines. J Immunol. 1993 Oct 1;151(7):3407–3419. [PubMed] [Google Scholar]
  4. Androlewicz M. J., Anderson K. S., Cresswell P. Evidence that transporters associated with antigen processing translocate a major histocompatibility complex class I-binding peptide into the endoplasmic reticulum in an ATP-dependent manner. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9130–9134. doi: 10.1073/pnas.90.19.9130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Arnold D., Driscoll J., Androlewicz M., Hughes E., Cresswell P., Spies T. Proteasome subunits encoded in the MHC are not generally required for the processing of peptides bound by MHC class I molecules. Nature. 1992 Nov 12;360(6400):171–174. doi: 10.1038/360171a0. [DOI] [PubMed] [Google Scholar]
  6. Attaya M., Jameson S., Martinez C. K., Hermel E., Aldrich C., Forman J., Lindahl K. F., Bevan M. J., Monaco J. J. Ham-2 corrects the class I antigen-processing defect in RMA-S cells. Nature. 1992 Feb 13;355(6361):647–649. doi: 10.1038/355647a0. [DOI] [PubMed] [Google Scholar]
  7. Baas E. J., van Santen H. M., Kleijmeer M. J., Geuze H. J., Peters P. J., Ploegh H. L. Peptide-induced stabilization and intracellular localization of empty HLA class I complexes. J Exp Med. 1992 Jul 1;176(1):147–156. doi: 10.1084/jem.176.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bailly E., Savel J., Mahouy G., Jaureguiberry G. Plasmodium falciparum: isolation and characterization of a 55-kDa protease with a cathepsin D-like activity from P. falciparum. Exp Parasitol. 1991 Apr;72(3):278–284. doi: 10.1016/0014-4894(91)90147-o. [DOI] [PubMed] [Google Scholar]
  9. Barnstable C. J., Bodmer W. F., Brown G., Galfre G., Milstein C., Williams A. F., Ziegler A. Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis. Cell. 1978 May;14(1):9–20. doi: 10.1016/0092-8674(78)90296-9. [DOI] [PubMed] [Google Scholar]
  10. Bearman R. M., Levine G. D., Bensch K. G. The ultrastructure of the normal human thymus: a study of 36 cases. Anat Rec. 1978 Mar;190(3):755–781. doi: 10.1002/ar.1091900310. [DOI] [PubMed] [Google Scholar]
  11. Bijlmakers M. J., Ploegh H. L. Putting together an MHC class I molecule. Curr Opin Immunol. 1993 Feb;5(1):21–26. doi: 10.1016/0952-7915(93)90076-5. [DOI] [PubMed] [Google Scholar]
  12. Blount P., Merlie J. P. Mutational analysis of muscle nicotinic acetylcholine receptor subunit assembly. J Cell Biol. 1990 Dec;111(6 Pt 1):2613–2622. doi: 10.1083/jcb.111.6.2613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Bonifacino J. S., Lippincott-Schwartz J. Degradation of proteins within the endoplasmic reticulum. Curr Opin Cell Biol. 1991 Aug;3(4):592–600. doi: 10.1016/0955-0674(91)90028-w. [DOI] [PubMed] [Google Scholar]
  14. Bonnerot C., Marks M. S., Cosson P., Robertson E. J., Bikoff E. K., Germain R. N., Bonifacino J. S. Association with BiP and aggregation of class II MHC molecules synthesized in the absence of invariant chain. EMBO J. 1994 Feb 15;13(4):934–944. doi: 10.1002/j.1460-2075.1994.tb06338.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. CLARK S. L., Jr The thymus in mice of strain 129/J, studied with the electron microscope. Am J Anat. 1963 Jan;112:1–33. doi: 10.1002/aja.1001120102. [DOI] [PubMed] [Google Scholar]
  16. Chen C., Bonifacino J. S., Yuan L. C., Klausner R. D. Selective degradation of T cell antigen receptor chains retained in a pre-Golgi compartment. J Cell Biol. 1988 Dec;107(6 Pt 1):2149–2161. doi: 10.1083/jcb.107.6.2149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Chin D. J., Luskey K. L., Anderson R. G., Faust J. R., Goldstein J. L., Brown M. S. Appearance of crystalloid endoplasmic reticulum in compactin-resistant Chinese hamster cells with a 500-fold increase in 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1185–1189. doi: 10.1073/pnas.79.4.1185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ciechanover A. The ubiquitin-proteasome proteolytic pathway. Cell. 1994 Oct 7;79(1):13–21. doi: 10.1016/0092-8674(94)90396-4. [DOI] [PubMed] [Google Scholar]
  19. DeMars R., Chang C. C., Shaw S., Reitnauer P. J., Sondel P. M. Homozygous deletions that simultaneously eliminate expressions of class I and class II antigens of EBV-transformed B-lymphoblastoid cells. I. Reduced proliferative responses of autologous and allogeneic T cells to mutant cells that have decreased expression of class II antigens. Hum Immunol. 1984 Oct;11(2):77–97. doi: 10.1016/0198-8859(84)90047-8. [DOI] [PubMed] [Google Scholar]
  20. Degen E., Williams D. B. Participation of a novel 88-kD protein in the biogenesis of murine class I histocompatibility molecules. J Cell Biol. 1991 Mar;112(6):1099–1115. doi: 10.1083/jcb.112.6.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Dick L. R., Aldrich C., Jameson S. C., Moomaw C. R., Pramanik B. C., Doyle C. K., DeMartino G. N., Bevan M. J., Forman J. M., Slaughter C. A. Proteolytic processing of ovalbumin and beta-galactosidase by the proteasome to a yield antigenic peptides. J Immunol. 1994 Apr 15;152(8):3884–3894. [PMC free article] [PubMed] [Google Scholar]
  22. Dunn W. A., Jr Studies on the mechanisms of autophagy: formation of the autophagic vacuole. J Cell Biol. 1990 Jun;110(6):1923–1933. doi: 10.1083/jcb.110.6.1923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hammond C., Helenius A. Quality control in the secretory pathway: retention of a misfolded viral membrane glycoprotein involves cycling between the ER, intermediate compartment, and Golgi apparatus. J Cell Biol. 1994 Jul;126(1):41–52. doi: 10.1083/jcb.126.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hauri H. P., Schweizer A. The endoplasmic reticulum-Golgi intermediate compartment. Curr Opin Cell Biol. 1992 Aug;4(4):600–608. doi: 10.1016/0955-0674(92)90078-Q. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Heemels M. T., Ploegh H. Generation, translocation, and presentation of MHC class I-restricted peptides. Annu Rev Biochem. 1995;64:463–491. doi: 10.1146/annurev.bi.64.070195.002335. [DOI] [PubMed] [Google Scholar]
  26. Hershko A., Ciechanover A. The ubiquitin system for protein degradation. Annu Rev Biochem. 1992;61:761–807. doi: 10.1146/annurev.bi.61.070192.003553. [DOI] [PubMed] [Google Scholar]
  27. Hobman T. C., Woodward L., Farquhar M. G. The rubella virus E1 glycoprotein is arrested in a novel post-ER, pre-Golgi compartment. J Cell Biol. 1992 Aug;118(4):795–811. doi: 10.1083/jcb.118.4.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Hochstrasser M. Ubiquitin, proteasomes, and the regulation of intracellular protein degradation. Curr Opin Cell Biol. 1995 Apr;7(2):215–223. doi: 10.1016/0955-0674(95)80031-x. [DOI] [PubMed] [Google Scholar]
  29. Howard J. C., Seelig A. Antigen processing. Peptides and the proteasome. Nature. 1993 Sep 16;365(6443):211–212. doi: 10.1038/365211a0. [DOI] [PubMed] [Google Scholar]
  30. Hurtley S. M., Helenius A. Protein oligomerization in the endoplasmic reticulum. Annu Rev Cell Biol. 1989;5:277–307. doi: 10.1146/annurev.cb.05.110189.001425. [DOI] [PubMed] [Google Scholar]
  31. Jamieson J. D., Palade G. E. Intracellular transport of secretory proteins in the pancreatic exocrine cell. I. Role of the peripheral elements of the Golgi complex. J Cell Biol. 1967 Aug;34(2):577–596. doi: 10.1083/jcb.34.2.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Janossy G., Thomas J. A., Bollum F. J., Granger S., Pizzolo G., Bradstock K. F., Wong L., McMichael A., Ganeshaguru K., Hoffbrand A. V. The human thymic microenvironment: an immunohistologic study. J Immunol. 1980 Jul;125(1):202–212. [PubMed] [Google Scholar]
  33. Kartenbeck J., Stukenbrok H., Helenius A. Endocytosis of simian virus 40 into the endoplasmic reticulum. J Cell Biol. 1989 Dec;109(6 Pt 1):2721–2729. doi: 10.1083/jcb.109.6.2721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Kavathas P., Bach F. H., DeMars R. Gamma ray-induced loss of expression of HLA and glyoxalase I alleles in lymphoblastoid cells. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4251–4255. doi: 10.1073/pnas.77.7.4251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Klausner R. D., Sitia R. Protein degradation in the endoplasmic reticulum. Cell. 1990 Aug 24;62(4):611–614. doi: 10.1016/0092-8674(90)90104-m. [DOI] [PubMed] [Google Scholar]
  36. Kleijmeer M. J., Kelly A., Geuze H. J., Slot J. W., Townsend A., Trowsdale J. Location of MHC-encoded transporters in the endoplasmic reticulum and cis-Golgi. Nature. 1992 May 28;357(6376):342–344. doi: 10.1038/357342a0. [DOI] [PubMed] [Google Scholar]
  37. Krijnse-Locker J., Ericsson M., Rottier P. J., Griffiths G. Characterization of the budding compartment of mouse hepatitis virus: evidence that transport from the RER to the Golgi complex requires only one vesicular transport step. J Cell Biol. 1994 Jan;124(1-2):55–70. doi: 10.1083/jcb.124.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Krimpenfort P., Rudenko G., Hochstenbach F., Guessow D., Berns A., Ploegh H. Crosses of two independently derived transgenic mice demonstrate functional complementation of the genes encoding heavy (HLA-B27) and light (beta 2-microglobulin) chains of HLA class I antigens. EMBO J. 1987 Jun;6(6):1673–1676. doi: 10.1002/j.1460-2075.1987.tb02416.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Kärre K., Ljunggren H. G., Piontek G., Kiessling R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature. 1986 Feb 20;319(6055):675–678. doi: 10.1038/319675a0. [DOI] [PubMed] [Google Scholar]
  40. Lippincott-Schwartz J., Bonifacino J. S., Yuan L. C., Klausner R. D. Degradation from the endoplasmic reticulum: disposing of newly synthesized proteins. Cell. 1988 Jul 15;54(2):209–220. doi: 10.1016/0092-8674(88)90553-3. [DOI] [PubMed] [Google Scholar]
  41. Ljunggren H. G., Kärre K. Host resistance directed selectively against H-2-deficient lymphoma variants. Analysis of the mechanism. J Exp Med. 1985 Dec 1;162(6):1745–1759. doi: 10.1084/jem.162.6.1745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Ljunggren H. G., Stam N. J., Ohlén C., Neefjes J. J., Höglund P., Heemels M. T., Bastin J., Schumacher T. N., Townsend A., Kärre K. Empty MHC class I molecules come out in the cold. Nature. 1990 Aug 2;346(6283):476–480. doi: 10.1038/346476a0. [DOI] [PubMed] [Google Scholar]
  43. Louvard D., Reggio H., Warren G. Antibodies to the Golgi complex and the rough endoplasmic reticulum. J Cell Biol. 1982 Jan;92(1):92–107. doi: 10.1083/jcb.92.1.92. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Machold R. P., Andrée S., Van Kaer L., Ljunggren H. G., Ploegh H. L. Peptide influences the folding and intracellular transport of free major histocompatibility complex class I heavy chains. J Exp Med. 1995 Mar 1;181(3):1111–1122. doi: 10.1084/jem.181.3.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Martien van Santen H., Woolsey A., Rickardt P. G., Van Kaer L., Baas E. J., Berns A., Tonegawa S., Ploegh H. L. Increase in positive selection of CD8+ T cells in TAP1-mutant mice by human beta 2-microglobulin transgene. J Exp Med. 1995 Feb 1;181(2):787–792. doi: 10.1084/jem.181.2.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Michalek M. T., Grant E. P., Gramm C., Goldberg A. L., Rock K. L. A role for the ubiquitin-dependent proteolytic pathway in MHC class I-restricted antigen presentation. Nature. 1993 Jun 10;363(6429):552–554. doi: 10.1038/363552a0. [DOI] [PubMed] [Google Scholar]
  47. Momburg F., Ortiz-Navarrete V., Neefjes J., Goulmy E., van de Wal Y., Spits H., Powis S. J., Butcher G. W., Howard J. C., Walden P. Proteasome subunits encoded by the major histocompatibility complex are not essential for antigen presentation. Nature. 1992 Nov 12;360(6400):174–177. doi: 10.1038/360174a0. [DOI] [PubMed] [Google Scholar]
  48. Neefjes J. J., Momburg F., Hämmerling G. J. Selective and ATP-dependent translocation of peptides by the MHC-encoded transporter. Science. 1993 Aug 6;261(5122):769–771. doi: 10.1126/science.8342042. [DOI] [PubMed] [Google Scholar]
  49. Neefjes J. J., Ploegh H. L. Allele and locus-specific differences in cell surface expression and the association of HLA class I heavy chain with beta 2-microglobulin: differential effects of inhibition of glycosylation on class I subunit association. Eur J Immunol. 1988 May;18(5):801–810. doi: 10.1002/eji.1830180522. [DOI] [PubMed] [Google Scholar]
  50. Noda T., Farquhar M. G. A non-autophagic pathway for diversion of ER secretory proteins to lysosomes. J Cell Biol. 1992 Oct;119(1):85–97. doi: 10.1083/jcb.119.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Oprins A., Duden R., Kreis T. E., Geuze H. J., Slot J. W. Beta-COP localizes mainly to the cis-Golgi side in exocrine pancreas. J Cell Biol. 1993 Apr;121(1):49–59. doi: 10.1083/jcb.121.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Orci L., Perrelet A., Ravazzola M., Wieland F. T., Schekman R., Rothman J. E. "BFA bodies": a subcompartment of the endoplasmic reticulum. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11089–11093. doi: 10.1073/pnas.90.23.11089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Pelham H. R. Control of protein exit from the endoplasmic reticulum. Annu Rev Cell Biol. 1989;5:1–23. doi: 10.1146/annurev.cb.05.110189.000245. [DOI] [PubMed] [Google Scholar]
  54. Peters P. J., Neefjes J. J., Oorschot V., Ploegh H. L., Geuze H. J. Segregation of MHC class II molecules from MHC class I molecules in the Golgi complex for transport to lysosomal compartments. Nature. 1991 Feb 21;349(6311):669–676. doi: 10.1038/349669a0. [DOI] [PubMed] [Google Scholar]
  55. Powis S. J., Townsend A. R., Deverson E. V., Bastin J., Butcher G. W., Howard J. C. Restoration of antigen presentation to the mutant cell line RMA-S by an MHC-linked transporter. Nature. 1991 Dec 19;354(6354):528–531. doi: 10.1038/354528a0. [DOI] [PubMed] [Google Scholar]
  56. Rabouille C., Strous G. J., Crapo J. D., Geuze H. J., Slot J. W. The differential degradation of two cytosolic proteins as a tool to monitor autophagy in hepatocytes by immunocytochemistry. J Cell Biol. 1993 Feb;120(4):897–908. doi: 10.1083/jcb.120.4.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Rock K. L., Gramm C., Rothstein L., Clark K., Stein R., Dick L., Hwang D., Goldberg A. L. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell. 1994 Sep 9;78(5):761–771. doi: 10.1016/s0092-8674(94)90462-6. [DOI] [PubMed] [Google Scholar]
  58. Rose J. K., Doms R. W. Regulation of protein export from the endoplasmic reticulum. Annu Rev Cell Biol. 1988;4:257–288. doi: 10.1146/annurev.cb.04.110188.001353. [DOI] [PubMed] [Google Scholar]
  59. Rouse R. V., van Ewijk W., Jones P. P., Weissman I. L. Expression of MHC antigens by mouse thymic dendritic cells. J Immunol. 1979 Jun;122(6):2508–2515. [PubMed] [Google Scholar]
  60. Schwartz A. L., Ciechanover A., Brandt R. A., Geuze H. J. Immunoelectron microscopic localization of ubiquitin in hepatoma cells. EMBO J. 1988 Oct;7(10):2961–2966. doi: 10.1002/j.1460-2075.1988.tb03158.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Schwartz A. L., Trausch J. S., Ciechanover A., Slot J. W., Geuze H. Immunoelectron microscopic localization of the ubiquitin-activating enzyme E1 in HepG2 cells. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5542–5546. doi: 10.1073/pnas.89.12.5542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Schweizer A., Fransen J. A., Bächi T., Ginsel L., Hauri H. P. Identification, by a monoclonal antibody, of a 53-kD protein associated with a tubulo-vesicular compartment at the cis-side of the Golgi apparatus. J Cell Biol. 1988 Nov;107(5):1643–1653. doi: 10.1083/jcb.107.5.1643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Schweizer A., Fransen J. A., Matter K., Kreis T. E., Ginsel L., Hauri H. P. Identification of an intermediate compartment involved in protein transport from endoplasmic reticulum to Golgi apparatus. Eur J Cell Biol. 1990 Dec;53(2):185–196. [PubMed] [Google Scholar]
  64. Shepherd J. C., Schumacher T. N., Ashton-Rickardt P. G., Imaeda S., Ploegh H. L., Janeway C. A., Jr, Tonegawa S. TAP1-dependent peptide translocation in vitro is ATP dependent and peptide selective. Cell. 1993 Aug 13;74(3):577–584. doi: 10.1016/0092-8674(93)80058-m. [DOI] [PubMed] [Google Scholar]
  65. Sitia R., Neuberger M. S., Milstein C. Regulation of membrane IgM expression in secretory B cells: translational and post-translational events. EMBO J. 1987 Dec 20;6(13):3969–3977. doi: 10.1002/j.1460-2075.1987.tb02739.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Slot J. W., Geuze H. J., Gigengack S., Lienhard G. E., James D. E. Immuno-localization of the insulin regulatable glucose transporter in brown adipose tissue of the rat. J Cell Biol. 1991 Apr;113(1):123–135. doi: 10.1083/jcb.113.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Smith M. H., Parker J. M., Hodges R. S., Barber B. H. The preparation and characterization of anti-peptide heteroantisera recognizing subregions of the intracytoplasmic domain of class I H-2 antigens. Mol Immunol. 1986 Oct;23(10):1077–1092. doi: 10.1016/0161-5890(86)90006-4. [DOI] [PubMed] [Google Scholar]
  68. Sodeik B., Doms R. W., Ericsson M., Hiller G., Machamer C. E., van 't Hof W., van Meer G., Moss B., Griffiths G. Assembly of vaccinia virus: role of the intermediate compartment between the endoplasmic reticulum and the Golgi stacks. J Cell Biol. 1993 May;121(3):521–541. doi: 10.1083/jcb.121.3.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Spies T., DeMars R. Restored expression of major histocompatibility class I molecules by gene transfer of a putative peptide transporter. Nature. 1991 May 23;351(6324):323–324. doi: 10.1038/351323a0. [DOI] [PubMed] [Google Scholar]
  70. Stam N. J., Spits H., Ploegh H. L. Monoclonal antibodies raised against denatured HLA-B locus heavy chains permit biochemical characterization of certain HLA-C locus products. J Immunol. 1986 Oct 1;137(7):2299–2306. [PubMed] [Google Scholar]
  71. Stam N. J., Vroom T. M., Peters P. J., Pastoors E. B., Ploegh H. L. HLA-A- and HLA-B-specific monoclonal antibodies reactive with free heavy chains in western blots, in formalin-fixed, paraffin-embedded tissue sections and in cryo-immuno-electron microscopy. Int Immunol. 1990;2(2):113–125. doi: 10.1093/intimm/2.2.113. [DOI] [PubMed] [Google Scholar]
  72. Townsend A., Elliott T., Cerundolo V., Foster L., Barber B., Tse A. Assembly of MHC class I molecules analyzed in vitro. Cell. 1990 Jul 27;62(2):285–295. doi: 10.1016/0092-8674(90)90366-m. [DOI] [PubMed] [Google Scholar]
  73. Tsao Y. S., Ivessa N. E., Adesnik M., Sabatini D. D., Kreibich G. Carboxy terminally truncated forms of ribophorin I are degraded in pre-Golgi compartments by a calcium-dependent process. J Cell Biol. 1992 Jan;116(1):57–67. doi: 10.1083/jcb.116.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Van Ewijk W. Immunohistology of lymphoid and non-lymphoid cells in the thymus in relation to T lymphocyte differentiation. Am J Anat. 1984 Jul;170(3):311–330. doi: 10.1002/aja.1001700307. [DOI] [PubMed] [Google Scholar]
  75. Van Ewijk W., Rouse R. V., Weissman I. L. Distribution of H-2 microenvironments in the mouse thymus. Immunoelectron microscopic identification of I-A and H-2K bearing cells. J Histochem Cytochem. 1980 Oct;28(10):1089–1099. doi: 10.1177/28.10.6999083. [DOI] [PubMed] [Google Scholar]
  76. Van Kaer L., Ashton-Rickardt P. G., Ploegh H. L., Tonegawa S. TAP1 mutant mice are deficient in antigen presentation, surface class I molecules, and CD4-8+ T cells. Cell. 1992 Dec 24;71(7):1205–1214. doi: 10.1016/s0092-8674(05)80068-6. [DOI] [PubMed] [Google Scholar]
  77. Vaux D., Tooze J., Fuller S. Identification by anti-idiotype antibodies of an intracellular membrane protein that recognizes a mammalian endoplasmic reticulum retention signal. Nature. 1990 Jun 7;345(6275):495–502. doi: 10.1038/345495a0. [DOI] [PubMed] [Google Scholar]
  78. Vertel B. M., Velasco A., LaFrance S., Walters L., Kaczman-Daniel K. Precursors of chondroitin sulfate proteoglycan are segregated within a subcompartment of the chondrocyte endoplasmic reticulum. J Cell Biol. 1989 Oct;109(4 Pt 1):1827–1836. doi: 10.1083/jcb.109.4.1827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Wikström L., Lodish H. F. Unfolded H2b asialoglycoprotein receptor subunit polypeptides are selectively degraded within the endoplasmic reticulum. J Biol Chem. 1993 Jul 5;268(19):14412–14416. [PubMed] [Google Scholar]
  80. Yewdell J. W., Bennink J. R. Cell biology of antigen processing and presentation to major histocompatibility complex class I molecule-restricted T lymphocytes. Adv Immunol. 1992;52:1–123. doi: 10.1016/s0065-2776(08)60875-5. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES