First Author | Prasanna SJ | Year | 2004 |
Journal | Mol Immunol | Volume | 41 |
Issue | 10 | Pages | 1029-45 |
PubMed ID | 15302165 | Mgi Jnum | J:92342 |
Mgi Id | MGI:3052409 | Doi | 10.1016/j.molimm.2004.05.007 |
Citation | Prasanna SJ, et al. (2004) The MHC-encoded class I molecule, H-2Kk, demonstrates distinct requirements of assembly factors for cell surface expression: roles of TAP, Tapasin and beta2-microglobulin. Mol Immunol 41(10):1029-45 |
abstractText | 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 degrees C. Immunoprecipitation experiments revealed that H-2Kk, H-2Dd and beta2-microglobulin (beta2m) 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 beta2m 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 beta2m-mediated H-2Dd levels. Secondly, Tapasin overexpression increases Tap2 transcripts and cooperates with TAPl or human beta2m 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-2Dd, a functional TAP is 'essential' for H-2Kk cell surface expression. |