Folding and Assembly of Major Histocompatibility Complex Class I Heterodimers in the Endoplasmic Reticulum of Intact Cells Precedes the Binding of Peptide

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1993 Dec 1

PMID 8245776

Citations 19

Authors

J J Neefjes

G J Hammerling

F Momburg

Affiliations

Soon will be listed here.

Abstract

Major histocompatibility complex (MHC) class I molecules are heterotrimers consisting of a polymorphic H chain, beta 2-microglobulin (beta 2m) and peptide. Peptides are thought to associate early during biosynthesis but the order of assembly of class I molecules from their component subunits in intact cells is not settled. We have studied the assembly of MHC class I molecules in intact cells with or without peptide transporters. MHC class I H chain/beta 2m heterodimers can be efficiently recovered only 4 min after translation and are preceded by a folding intermediate. Approximately 2 min after their formation, the class I heterodimers are loaded with peptides resulting in stable class I heterotrimers. In these in vivo studies, no evidence was obtained that peptide binding to the H chain preceded the association with beta 2m. In contrast, nonassembled class I H chains could be recovered immediately after translation, but this pool did not participate in the formation of class I molecules.

Citing Articles

Impacts of combining anti-PD-L1 immunotherapy and radiotherapy on the tumour immune microenvironment in a murine prostate cancer model.

Philippou Y, Sjoberg H, Murphy E, Alyacoubi S, Jones K, Gordon-Weeks A Br J Cancer. 2020; 123(7):1089-1100.

PMID: 32641865 PMC: 7525450. DOI: 10.1038/s41416-020-0956-x.

Strict Assembly Restriction of Peptides from Rabbit Hemorrhagic Disease Virus Presented by Rabbit Major Histocompatibility Complex Class I Molecule RLA-A1.

Zhang Q, Liu K, Yue C, Zhang D, Lu D, Xiao W J Virol. 2020; 94(17).

PMID: 32522857 PMC: 7431782. DOI: 10.1128/JVI.00396-20.

The first step of peptide selection in antigen presentation by MHC class I molecules.

Garstka M, Fish A, Celie P, Joosten R, Janssen G, Berlin I Proc Natl Acad Sci U S A. 2015; 112(5):1505-10.

PMID: 25605945 PMC: 4321303. DOI: 10.1073/pnas.1416543112.

A negative feedback modulator of antigen processing evolved from a frameshift in the cowpox virus genome.

Lin J, Eggensperger S, Hank S, Wycisk A, Wieneke R, Mayerhofer P PLoS Pathog. 2014; 10(12):e1004554.

PMID: 25503639 PMC: 4263761. DOI: 10.1371/journal.ppat.1004554.

Pulse-chase analysis for studies of MHC class II biosynthesis, maturation, and peptide loading.

Hou T, Rinderknecht C, Hadjinicolaou A, Busch R, Mellins E Methods Mol Biol. 2013; 960:411-432.

PMID: 23329504 PMC: 4159250. DOI: 10.1007/978-1-62703-218-6_31.

References

Myers N, Lie W, Nett M, Rubocki R, Hansen T . The conformation of Ld induced by beta 2-microglobulin is fixed during de novo synthesis and irreversible by exchange or dissociation. J Immunol. 1989; 142(8):2751-8. View

Neefjes J, Ploegh H . 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; 18(5):801-10. DOI: 10.1002/eji.1830180522. View

Lie W, Myers N, Gorka J, Rubocki R, Connolly J, Hansen T . Peptide ligand-induced conformation and surface expression of the Ld class I MHC molecule. Nature. 1990; 344(6265):439-41. DOI: 10.1038/344439a0. View

Ljunggren H, Stam N, Ohlen C, Neefjes J, Hoglund P, Heemels M . Empty MHC class I molecules come out in the cold. Nature. 1990; 346(6283):476-80. DOI: 10.1038/346476a0. View

Perarnau B, Siegrist C, Gillet A, Vincent C, Kimura S, Lemonnier F . Beta 2-microglobulin restriction of antigen presentation. Nature. 1990; 346(6286):751-4. DOI: 10.1038/346751a0. View

Falk K, Rotzschke O, Rammensee H . Cellular peptide composition governed by major histocompatibility complex class I molecules. Nature. 1990; 348(6298):248-51. DOI: 10.1038/348248a0. View

Kvist S, Hamann U . A nucleoprotein peptide of influenza A virus stimulates assembly of HLA-B27 class I heavy chains and beta 2-microglobulin translated in vitro. Nature. 1990; 348(6300):446-8. DOI: 10.1038/348446a0. View

Rock K, GAMBLE S, Rothstein L, Gramm C, Benacerraf B . Dissociation of beta 2-microglobulin leads to the accumulation of a substantial pool of inactive class I MHC heavy chains on the cell surface. Cell. 1991; 65(4):611-20. DOI: 10.1016/0092-8674(91)90093-e. View

Elliott T, Cerundolo V, Elvin J, Townsend A . Peptide-induced conformational change of the class I heavy chain. Nature. 1991; 351(6325):402-6. DOI: 10.1038/351402a0. View

10.

Braakman I, Wagner K, Helenius A . Folding of influenza hemagglutinin in the endoplasmic reticulum. J Cell Biol. 1991; 114(3):401-11. PMC: 2289100. DOI: 10.1083/jcb.114.3.401. View

11.

Hsu V, Yuan L, Nuchtern J, Lippincott-Schwartz J, Hammerling G, Klausner R . A recycling pathway between the endoplasmic reticulum and the Golgi apparatus for retention of unassembled MHC class I molecules. Nature. 1991; 352(6334):441-4. DOI: 10.1038/352441a0. View

12.

Levy F, Gabathuler R, Larsson R, Kvist S . ATP is required for in vitro assembly of MHC class I antigens but not for transfer of peptides across the ER membrane. Cell. 1991; 67(2):265-74. DOI: 10.1016/0092-8674(91)90178-2. View

13.

Levy F, Larsson R, Kvist S . Translocation of peptides through microsomal membranes is a rapid process and promotes assembly of HLA-B27 heavy chain and beta 2-microglobulin translated in vitro. J Cell Biol. 1991; 115(4):959-70. PMC: 2289957. DOI: 10.1083/jcb.115.4.959. View

14.

Henderson R, Michel H, Sakaguchi K, Shabanowitz J, Appella E, Hunt D . HLA-A2.1-associated peptides from a mutant cell line: a second pathway of antigen presentation. Science. 1992; 255(5049):1264-6. DOI: 10.1126/science.1546329. View

15.

Wei M, Cresswell P . HLA-A2 molecules in an antigen-processing mutant cell contain signal sequence-derived peptides. Nature. 1992; 356(6368):443-6. DOI: 10.1038/356443a0. View

16.

DEGEN E, Williams D . Efficient dissociation of the p88 chaperone from major histocompatibility complex class I molecules requires both beta 2-microglobulin and peptide. J Exp Med. 1992; 175(6):1653-61. PMC: 2119236. DOI: 10.1084/jem.175.6.1653. View

17.

Baas E, van Santen H, Kleijmeer M, Geuze H, Peters P, Ploegh H . Peptide-induced stabilization and intracellular localization of empty HLA class I complexes. J Exp Med. 1992; 176(1):147-56. PMC: 2119279. DOI: 10.1084/jem.176.1.147. View

18.

Fremont D, Matsumura M, Stura E, Peterson P, Wilson I . Crystal structures of two viral peptides in complex with murine MHC class I H-2Kb. Science. 1992; 257(5072):919-27. DOI: 10.1126/science.1323877. View

19.

Madden D, Gorga J, Strominger J, Wiley D . The three-dimensional structure of HLA-B27 at 2.1 A resolution suggests a general mechanism for tight peptide binding to MHC. Cell. 1992; 70(6):1035-48. DOI: 10.1016/0092-8674(92)90252-8. View

20.

Galvin K, Krishna S, Ponchel F, Frohlich M, Cummings D, Carlson R . The major histocompatibility complex class I antigen-binding protein p88 is the product of the calnexin gene. Proc Natl Acad Sci U S A. 1992; 89(18):8452-6. PMC: 49938. DOI: 10.1073/pnas.89.18.8452. View