PMID- 10748183 OWN - NLM STAT- MEDLINE DCOM- 20000711 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 275 IP - 22 DP - 2000 Jun 2 TI - Dependence of elevated human leukocyte antigen class I molecule expression on increased heavy chain, light chain (beta 2-microglobulin), transporter associated with antigen processing, tapasin, and peptide. PG - 16643-9 AB - Human leukocyte antigen (HLA) class I molecule expression was investigated by DNA-mediated gene transfer. Cell surface expression was increased up to 75% by transfection of HLA-A2 or HLA-B8 heavy chain genes but not genes encoding light chains (beta(2)-microglobulin (beta(2)m)), transporter associated with antigen processing (TAP), or tapasin. Interferon (IFN) treatment further increased expression of transfected heavy chains, suggesting that IFN inducible molecules support heavy chain expression. IFN induces beta(2)m, TAP, and tapasin mRNAs. Transfected heavy chain expression increased upon cotransfection with genes encoding TAP1 and TAP2 but not individual TAP subunits, beta(2)m, or tapasin. Tetracycline inducible heavy chain gene expression was also increased by IFN treatment or TAP cotransfection, suggesting that IFN-induced TAP supports heavy chain maturation. Expression of a mutant that does not interact strongly with TAP, HLA-A2-T134K, was also increased by IFN. Inhibition of TAP-dependent peptide transport by ICP47 reduced heavy chain expression. Expression of HLA-A2, but not HLA-B8, was restored in ICP47 cells by HLA-A2-binding (IP-30) signal peptides. However, these peptides did not further increase transfected HLA-A2 expression, suggesting that peptide availability does not limit heavy chain expression in the absence of ICP47. These results suggest that cytokine-induced TAP supports maturation of HLA class I molecules through combined chaperone and peptide supply functions. FAU - Johnson, D R AU - Johnson DR AD - Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. david.johnson@yale.edu FAU - Mook-Kanamori, B AU - Mook-Kanamori B LA - eng GR - R29-AI35099/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Antiporters) RN - 0 (Carrier Proteins) RN - 0 (DNA Primers) RN - 0 (HLA-A2 Antigen) RN - 0 (HLA-B8 Antigen) RN - 0 (Immunoglobulins) RN - 0 (Membrane Transport Proteins) RN - 0 (Protein Sorting Signals) RN - 0 (Proteins) RN - 0 (beta 2-Microglobulin) RN - 0 (tapasin) RN - EC 1.- (Oxidoreductases) RN - EC 1.8.- (IFI30 protein, human) RN - EC 1.8.- (Oxidoreductases Acting on Sulfur Group Donors) SB - IM MH - Antiporters/*metabolism MH - Base Sequence MH - Carrier Proteins/*metabolism MH - DNA Primers MH - HLA-A2 Antigen/*genetics MH - HLA-B8 Antigen/*genetics MH - HeLa Cells MH - Humans MH - Immunoglobulins/*metabolism MH - Membrane Transport Proteins MH - *Oxidoreductases MH - Oxidoreductases Acting on Sulfur Group Donors MH - Protein Sorting Signals/*metabolism MH - Proteins/metabolism MH - Transfection MH - beta 2-Microglobulin/*metabolism EDAT- 2000/04/05 09:00 MHDA- 2000/07/15 11:00 CRDT- 2000/04/05 09:00 PHST- 2000/04/05 09:00 [pubmed] PHST- 2000/07/15 11:00 [medline] PHST- 2000/04/05 09:00 [entrez] AID - S0021-9258(19)80255-7 [pii] AID - 10.1074/jbc.M910035199 [doi] PST - ppublish SO - J Biol Chem. 2000 Jun 2;275(22):16643-9. doi: 10.1074/jbc.M910035199.