The MHC-encoded class I molecule, H-2Kk, demonstrates distinct requirements of assembly factors for cell surface expression

Roles of TAP, Tapasin and β2-microglobulin

S. Jyothi Prasanna, Dipankar Nandi

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9 Citations (Scopus)

Abstract

Major histocompatibility complex encoded class I (MHC-I) molecules display peptides derived from endogenous proteins for perusal by CD8+ T lymphocytes. H6, a mouse hepatoma cell line, expresses low levels of surface H-2Dd but not H-2Kk. Surface H-2Dd molecules are unstable and their levels, but not H-2Kk, are induced at 22°C. Immunoprecipitation experiments revealed that H-2Kk, H-2Dd and β2-microglobulin (β2m) are expressed intracellularly; however no conformed MHC-I are present. Transcriptional profiling of factors required for MHC-I assembly demonstrated greatly reduced levels of the Transporter associated with antigen processing (Tap)2 subunit. The role of key assembly molecules in the MHC-I pathway was investigated by ectopic expression studies. Overexpression of β2m enhanced surface H-2Dd, but not H-2Kk, levels whereas overexpression of TAP2 rescued surface H-2Kk, but not H-2Dd, levels. Interestingly, Tapasin plays a dual role: first, in quality control by reducing the induced surface expression of TAP2-mediated H-2Kk and β2m-mediated H-2Dd levels. Secondly, Tapasin overexpression increases Tap2 transcripts and cooperates with TAPl or human β2m to enhance surface H-2Kk expression; this synergy is TAP-dependent as demonstrated by infected cell protein 47 (ICP47) inhibition studies. Unlike the well studied H-2 MHC-I alleles, H-2Kb, H-2Db, H-2Kd and H-2D d, a functional TAP is "essential" for H-2Kk cell surface expression.

Original languageEnglish
Pages (from-to)1029-1045
Number of pages17
JournalMolecular Immunology
Volume41
Issue number10
DOIs
Publication statusPublished - 08-2004

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Major Histocompatibility Complex
Antigen Presentation
Immunoprecipitation
Quality Control
Hepatocellular Carcinoma
Proteins
Alleles
tapasin
T-Lymphocytes
Cell Line
Peptides

All Science Journal Classification (ASJC) codes

  • Immunology
  • Molecular Biology

Cite this

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title = "The MHC-encoded class I molecule, H-2Kk, demonstrates distinct requirements of assembly factors for cell surface expression: Roles of TAP, Tapasin and β2-microglobulin",
abstract = "Major histocompatibility complex encoded class I (MHC-I) molecules display peptides derived from endogenous proteins for perusal by CD8+ T lymphocytes. H6, a mouse hepatoma cell line, expresses low levels of surface H-2Dd but not H-2Kk. Surface H-2Dd molecules are unstable and their levels, but not H-2Kk, are induced at 22°C. Immunoprecipitation experiments revealed that H-2Kk, H-2Dd and β2-microglobulin (β2m) are expressed intracellularly; however no conformed MHC-I are present. Transcriptional profiling of factors required for MHC-I assembly demonstrated greatly reduced levels of the Transporter associated with antigen processing (Tap)2 subunit. The role of key assembly molecules in the MHC-I pathway was investigated by ectopic expression studies. Overexpression of β2m enhanced surface H-2Dd, but not H-2Kk, levels whereas overexpression of TAP2 rescued surface H-2Kk, but not H-2Dd, levels. Interestingly, Tapasin plays a dual role: first, in quality control by reducing the induced surface expression of TAP2-mediated H-2Kk and β2m-mediated H-2Dd levels. Secondly, Tapasin overexpression increases Tap2 transcripts and cooperates with TAPl or human β2m to enhance surface H-2Kk expression; this synergy is TAP-dependent as demonstrated by infected cell protein 47 (ICP47) inhibition studies. Unlike the well studied H-2 MHC-I alleles, H-2Kb, H-2Db, H-2Kd and H-2D d, a functional TAP is {"}essential{"} for H-2Kk cell surface expression.",
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T1 - The MHC-encoded class I molecule, H-2Kk, demonstrates distinct requirements of assembly factors for cell surface expression

T2 - Roles of TAP, Tapasin and β2-microglobulin

AU - Prasanna, S. Jyothi

AU - Nandi, Dipankar

PY - 2004/8

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N2 - Major histocompatibility complex encoded class I (MHC-I) molecules display peptides derived from endogenous proteins for perusal by CD8+ T lymphocytes. H6, a mouse hepatoma cell line, expresses low levels of surface H-2Dd but not H-2Kk. Surface H-2Dd molecules are unstable and their levels, but not H-2Kk, are induced at 22°C. Immunoprecipitation experiments revealed that H-2Kk, H-2Dd and β2-microglobulin (β2m) are expressed intracellularly; however no conformed MHC-I are present. Transcriptional profiling of factors required for MHC-I assembly demonstrated greatly reduced levels of the Transporter associated with antigen processing (Tap)2 subunit. The role of key assembly molecules in the MHC-I pathway was investigated by ectopic expression studies. Overexpression of β2m enhanced surface H-2Dd, but not H-2Kk, levels whereas overexpression of TAP2 rescued surface H-2Kk, but not H-2Dd, levels. Interestingly, Tapasin plays a dual role: first, in quality control by reducing the induced surface expression of TAP2-mediated H-2Kk and β2m-mediated H-2Dd levels. Secondly, Tapasin overexpression increases Tap2 transcripts and cooperates with TAPl or human β2m to enhance surface H-2Kk expression; this synergy is TAP-dependent as demonstrated by infected cell protein 47 (ICP47) inhibition studies. Unlike the well studied H-2 MHC-I alleles, H-2Kb, H-2Db, H-2Kd and H-2D d, a functional TAP is "essential" for H-2Kk cell surface expression.

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