The MHC-encoded class I molecule, $H-2K^k$, demonstrates distinct requirements of assembly factors for cell surface expression: roles of TAP, Tapasin and ${\beta}_2$-microglobulin

Prasanna, Jyothi S and Nandi, Dipankar (2004) The MHC-encoded class I molecule, $H-2K^k$, demonstrates distinct requirements of assembly factors for cell surface expression: roles of TAP, Tapasin and ${\beta}_2$-microglobulin. In: Molecular Immunology, 41 (10). pp. 1029-1045.

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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 $H-2D^d$ but not $H-2K^k$. Surface $H-2D^d$ molecules are unstable and their levels, but not $H-2K^k$, are induced at $22^{\circ}C$. Immunoprecipitation experiments revealed that $H-2K^k$, $H-2D^d$ and ${\beta}_2$-microglobulin $({\beta}_2m)$ 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 ${\beta}_2m$ enhanced surface $H-2D^d$, but not $H-2K^k$, levels whereas overexpression of TAP2 rescued surface $H-2K^k$, but not $H-2D^d$, levels. Interestingly, Tapasin plays a dual role: first, in quality control by reducing the induced surface expression of TAP2-mediated $H-2K^k$ and ${\beta}_2m$-mediated $H-2D^d$ levels. Secondly, Tapasin overexpression increases Tap2 transcripts and cooperates with TAPl or human ${\beta}_2m$ to enhance surface $H-2K^k$ 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, $H-2K^b$, $H-2D^b$, $H-2K^d$ and $H-2D^d$, a functional TAP is "essential" for $H-2K^k$ cell surface expression.

Item Type:	Journal Article
Publication:	Molecular Immunology
Publisher:	Elsevier Ltd
Additional Information:	Copyright for this article belongs to Elsevier Ltd.
Keywords:	H-2 alleles;MHC-I trafficking;Folding and stability;Assembly factors;Chaperones
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	20 Nov 2007
Last Modified:	19 Sep 2010 04:17
URI:	http://eprints.iisc.ac.in/id/eprint/2347

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