• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Nov 15, 1991; 88(22): 10094–10098.

Two putative subunits of a peptide pump encoded in the human major histocompatibility complex class II region.


The class II region of the human major histocompatibility complex (MHC) may encode several genes controlling the processing of endogenous antigen and the presentation of peptide epitopes by MHC class I molecules to cytotoxic T lymphocytes. A previously described peptide supply factor (PSF1) is a member of the multidrug-resistance family of transporters and may pump cytosolic peptides into the membrane-bound compartment where class I molecules assemble. A second transporter gene, PSF2, was identified 10 kilobases (kb) from PSF1, near the class II DOB gene. The complete sequences of PSF1 and PSF2 were determined from cDNA clones. The translation products are closely related in sequence and predicted secondary structure. Both contain a highly conserved ATP-binding fold and share 25% homology in a hydrophobic domain with a tentative number of eight membrane-spanning segments. Based on the principle dimeric organization of these two domains in other transporters, PSF1 and PSF2 may function as complementary subunits, independently as homodimers, or both. Taken together with previous genetic evidence, the coregulation of PSF1 and PSF2 by gamma interferon and the to-some-degree coordinate transcription of these genes suggest a common role in peptide-loading of class I molecules, although a distinct function of PSF2 cannot be ruled out.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Townsend A, Bodmer H. Antigen recognition by class I-restricted T lymphocytes. Annu Rev Immunol. 1989;7:601–624. [PubMed]
  • Bjorkman PJ, Parham P. Structure, function, and diversity of class I major histocompatibility complex molecules. Annu Rev Biochem. 1990;59:253–288. [PubMed]
  • Moore MW, Carbone FR, Bevan MJ. Introduction of soluble protein into the class I pathway of antigen processing and presentation. Cell. 1988 Sep 9;54(6):777–785. [PubMed]
  • Sweetser MT, Morrison LA, Braciale VL, Braciale TJ. Recognition of pre-processed endogenous antigen by class I but not class II MHC-restricted T cells. Nature. 1989 Nov 9;342(6246):180–182. [PubMed]
  • Townsend A, Ohlén C, Bastin J, Ljunggren HG, Foster L, Kärre K. Association of class I major histocompatibility heavy and light chains induced by viral peptides. Nature. 1989 Aug 10;340(6233):443–448. [PubMed]
  • Nuchtern JG, Bonifacino JS, Biddison WE, Klausner RD. Brefeldin A implicates egress from endoplasmic reticulum in class I restricted antigen presentation. Nature. 1989 May 18;339(6221):223–226. [PubMed]
  • Yewdell JW, Bennink JR. Brefeldin A specifically inhibits presentation of protein antigens to cytotoxic T lymphocytes. Science. 1989 Jun 2;244(4908):1072–1075. [PubMed]
  • Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987 Oct 8;329(6139):512–518. [PubMed]
  • Van Bleek GM, Nathenson SG. Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kb molecule. Nature. 1990 Nov 15;348(6298):213–216. [PubMed]
  • Falk K, Rötzschke O, Stevanović S, Jung G, Rammensee HG. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature. 1991 May 23;351(6324):290–296. [PubMed]
  • DeMars R, Rudersdorf R, Chang C, Petersen J, Strandtmann J, Korn N, Sidwell B, Orr HT. Mutations that impair a posttranscriptional step in expression of HLA-A and -B antigens. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8183–8187. [PMC free article] [PubMed]
  • Salter RD, Cresswell P. Impaired assembly and transport of HLA-A and -B antigens in a mutant TxB cell hybrid. EMBO J. 1986 May;5(5):943–949. [PMC free article] [PubMed]
  • Cerundolo V, Alexander J, Anderson K, Lamb C, Cresswell P, McMichael A, Gotch F, Townsend A. Presentation of viral antigen controlled by a gene in the major histocompatibility complex. Nature. 1990 May 31;345(6274):449–452. [PubMed]
  • Hosken NA, Bevan MJ. Defective presentation of endogenous antigen by a cell line expressing class I molecules. Science. 1990 Apr 20;248(4953):367–370. [PubMed]
  • Spies T, Bresnahan M, Bahram S, Arnold D, Blanck G, Mellins E, Pious D, DeMars R. A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway. Nature. 1990 Dec 20;348(6303):744–747. [PubMed]
  • Spies T, DeMars R. Restored expression of major histocompatibility class I molecules by gene transfer of a putative peptide transporter. Nature. 1991 May 23;351(6324):323–324. [PubMed]
  • Anderson K, Cresswell P, Gammon M, Hermes J, Williamson A, Zweerink H. Endogenously synthesized peptide with an endoplasmic reticulum signal sequence sensitizes antigen processing mutant cells to class I-restricted cell-mediated lysis. J Exp Med. 1991 Aug 1;174(2):489–492. [PMC free article] [PubMed]
  • Trowsdale J, Hanson I, Mockridge I, Beck S, Townsend A, Kelly A. Sequences encoded in the class II region of the MHC related to the 'ABC' superfamily of transporters. Nature. 1990 Dec 20;348(6303):741–744. [PubMed]
  • Chen CJ, Chin JE, Ueda K, Clark DP, Pastan I, Gottesman MM, Roninson IB. Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell. 1986 Nov 7;47(3):381–389. [PubMed]
  • Gerlach JH, Endicott JA, Juranka PF, Henderson G, Sarangi F, Deuchars KL, Ling V. Homology between P-glycoprotein and a bacterial haemolysin transport protein suggests a model for multidrug resistance. Nature. 1986 Dec 4;324(6096):485–489. [PubMed]
  • Ueda K, Cardarelli C, Gottesman MM, Pastan I. Expression of a full-length cDNA for the human "MDR1" gene confers resistance to colchicine, doxorubicin, and vinblastine. Proc Natl Acad Sci U S A. 1987 May;84(9):3004–3008. [PMC free article] [PubMed]
  • Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou JL, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989 Sep 8;245(4922):1066–1073. [PubMed]
  • Kamijo K, Taketani S, Yokota S, Osumi T, Hashimoto T. The 70-kDa peroxisomal membrane protein is a member of the Mdr (P-glycoprotein)-related ATP-binding protein superfamily. J Biol Chem. 1990 Mar 15;265(8):4534–4540. [PubMed]
  • Kuchler K, Sterne RE, Thorner J. Saccharomyces cerevisiae STE6 gene product: a novel pathway for protein export in eukaryotic cells. EMBO J. 1989 Dec 20;8(13):3973–3984. [PMC free article] [PubMed]
  • McGrath JP, Varshavsky A. The yeast STE6 gene encodes a homologue of the mammalian multidrug resistance P-glycoprotein. Nature. 1989 Aug 3;340(6232):400–404. [PubMed]
  • Blight MA, Holland IB. Structure and function of haemolysin B,P-glycoprotein and other members of a novel family of membrane translocators. Mol Microbiol. 1990 Jun;4(6):873–880. [PubMed]
  • Higgins CF, Hiles ID, Salmond GP, Gill DR, Downie JA, Evans IJ, Holland IB, Gray L, Buckel SD, Bell AW, et al. A family of related ATP-binding subunits coupled to many distinct biological processes in bacteria. Nature. 1986 Oct 2;323(6087):448–450. [PubMed]
  • Hiles ID, Gallagher MP, Jamieson DJ, Higgins CF. Molecular characterization of the oligopeptide permease of Salmonella typhimurium. J Mol Biol. 1987 May 5;195(1):125–142. [PubMed]
  • Hyde SC, Emsley P, Hartshorn MJ, Mimmack MM, Gileadi U, Pearce SR, Gallagher MP, Gill DR, Hubbard RE, Higgins CF. Structural model of ATP-binding proteins associated with cystic fibrosis, multidrug resistance and bacterial transport. Nature. 1990 Jul 26;346(6282):362–365. [PubMed]
  • Nepom GT, Erlich H. MHC class-II molecules and autoimmunity. Annu Rev Immunol. 1991;9:493–525. [PubMed]
  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. [PubMed]
  • Feng DF, Doolittle RF. Progressive sequence alignment as a prerequisite to correct phylogenetic trees. J Mol Evol. 1987;25(4):351–360. [PubMed]
  • Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. [PubMed]
  • Monaco JJ, Cho S, Attaya M. Transport protein genes in the murine MHC: possible implications for antigen processing. Science. 1990 Dec 21;250(4988):1723–1726. [PubMed]
  • Deverson EV, Gow IR, Coadwell WJ, Monaco JJ, Butcher GW, Howard JC. MHC class II region encoding proteins related to the multidrug resistance family of transmembrane transporters. Nature. 1990 Dec 20;348(6303):738–741. [PubMed]
  • Eisenberg D. Three-dimensional structure of membrane and surface proteins. Annu Rev Biochem. 1984;53:595–623. [PubMed]
  • Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. [PMC free article] [PubMed]
  • Walker JE, Saraste M, Runswick MJ, Gay NJ. Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J. 1982;1(8):945–951. [PMC free article] [PubMed]
  • Horio M, Gottesman MM, Pastan I. ATP-dependent transport of vinblastine in vesicles from human multidrug-resistant cells. Proc Natl Acad Sci U S A. 1988 May;85(10):3580–3584. [PMC free article] [PubMed]
  • Azzaria M, Schurr E, Gros P. Discrete mutations introduced in the predicted nucleotide-binding sites of the mdr1 gene abolish its ability to confer multidrug resistance. Mol Cell Biol. 1989 Dec;9(12):5289–5297. [PMC free article] [PubMed]
  • Cutting GR, Kasch LM, Rosenstein BJ, Zielenski J, Tsui LC, Antonarakis SE, Kazazian HH., Jr A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein. Nature. 1990 Jul 26;346(6282):366–369. [PubMed]
  • Wang RC, Seror SJ, Blight M, Pratt JM, Broome-Smith JK, Holland IB. Analysis of the membrane organization of an Escherichia coli protein translocator, HlyB, a member of a large family of prokaryote and eukaryote surface transport proteins. J Mol Biol. 1991 Feb 5;217(3):441–454. [PubMed]
  • van der Bliek AM, Kooiman PM, Schneider C, Borst P. Sequence of mdr3 cDNA encoding a human P-glycoprotein. Gene. 1988 Nov 30;71(2):401–411. [PubMed]
  • Buschman E, Gros P. Functional analysis of chimeric genes obtained by exchanging homologous domains of the mouse mdr1 and mdr2 genes. Mol Cell Biol. 1991 Feb;11(2):595–603. [PMC free article] [PubMed]
  • Choi KH, Chen CJ, Kriegler M, Roninson IB. An altered pattern of cross-resistance in multidrug-resistant human cells results from spontaneous mutations in the mdr1 (P-glycoprotein) gene. Cell. 1988 May 20;53(4):519–529. [PubMed]
  • Foote SJ, Kyle DE, Martin RK, Oduola AM, Forsyth K, Kemp DJ, Cowman AF. Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum. Nature. 1990 May 17;345(6272):255–258. [PubMed]
  • Bruggemann EP, Germann UA, Gottesman MM, Pastan I. Two different regions of P-glycoprotein [corrected] are photoaffinity-labeled by azidopine. J Biol Chem. 1989 Sep 15;264(26):15483–15488. [PubMed]
  • Shin J, Dunbrack RL, Jr, Lee S, Strominger JL. Signals for retention of transmembrane proteins in the endoplasmic reticulum studied with CD4 truncation mutants. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1918–1922. [PMC free article] [PubMed]
  • Mellins E, Smith L, Arp B, Cotner T, Celis E, Pious D. Defective processing and presentation of exogenous antigens in mutants with normal HLA class II genes. Nature. 1990 Jan 4;343(6253):71–74. [PubMed]
  • Livingstone AM, Powis SJ, Diamond AG, Butcher GW, Howard JC. A trans-acting major histocompatibility complex-linked gene whose alleles determine gain and loss changes in the antigenic structure of a classical class I molecule. J Exp Med. 1989 Sep 1;170(3):777–795. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

  • Natural Polymorphisms in Tap2 Influence Negative Selection and CD4:CD8 Lineage Commitment in the Rat[PLoS Genetics. ]
    Tuncel J, Haag S, Yau AC, Norin U, Baud A, Lönnblom E, Maratou K, Ytterberg AJ, Ekman D, Thordardottir S, Johannesson M, Gillett A, EURATRANS Consortium, Stridh P, Jagodic M, Olsson T, Fernández-Teruel A, Zubarev RA, Mott R, Aitman TJ, Flint J, Holmdahl R. PLoS Genetics. 10(2)e1004151
  • Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis[American Journal of Human Genetics. 2014]
    Mayes MD, Bossini-Castillo L, Gorlova O, Martin JE, Zhou X, Chen WV, Assassi S, Ying J, Tan FK, Arnett FC, Reveille JD, Guerra S, Teruel M, Carmona FD, Gregersen PK, Lee AT, López-Isac E, Ochoa E, Carreira P, Simeón CP, Castellví I, González-Gay MÁ, the Spanish Scleroderma Groupthe Spanish Scleroderma GroupOrtego-CentenoNorbertoNRíosRaquelRCallejasJosé LuisJLNavarreteNuriaNGarcía PortalesRosaRCampsMaría TeresaMTFernández-NebroAntonioAGonzález-EscribanoMaría F.MFSánchez-RománJulioJGarcía-HernándezFrancisco JoséFJCastilloMaría JesúsMJAguirreMaría ÁngelesMÁGómez-GraciaInmaculadaIFernández-GutiérrezBenjamínBRodríguez-RodríguezLuisLVicenteEstherEAndreuJosé LuisJLFernández de CastroMónicaMGarcía de la PeñaPalomaPLópez-LongoFrancisco JavierFJMartínezLinaLFonollosaVicenteVEspinosaGerardGTolosaCarlosCProsAnnaARodríguez CarballeiraMónicaMNarváezFrancisco JavierFJRubio RivasManelMOrtiz SantamaríaVeraVDíazBernardinoBTrapiellaLuisLFreireMaría del CarmenMDSousaAdriánAEgurbideMaría VictoriaMVFanlo MateoPatriciaPSáez-CometLuisLDíazFedericoFHernándezVanesaVBeltránEmmaERomán-IvorraJosé AndrésJAGrauElenaEAlegre SanchoJuan JoséJJBlanco GarcíaFrancisco J.FJOreiroNatividadNFernández SueiroLuisL, Zhernakova A, Padyukov L, Alarcón-Riquelme M, Wijmenga C, Brown M, Beretta L, Riemekasten G, Witte T, Hunzelmann N, Kreuter A, Distler JH, Voskuyl AE, Schuerwegh AJ, Hesselstrand R, Nordin A, Airó P, Lunardi C, Shiels P, van Laar JM, Herrick A, Worthington J, Denton C, Wigley FM, Hummers LK, Varga J, Hinchcliff ME, Baron M, Hudson M, Pope JE, Furst DE, Khanna D, Phillips K, Schiopu E, Segal BM, Molitor JA, Silver RM, Steen VD, Simms RW, Lafyatis RA, Fessler BJ, Frech TM, AlKassab F, Docherty P, Kaminska E, Khalidi N, Jones HN, Markland J, Robinson D, Broen J, Radstake TR, Fonseca C, Koeleman BP, Martin J. American Journal of Human Genetics. 2014 Jan 2; 94(1)47-61
  • A DNA Methylation Network Interaction Measure, and Detection of Network Oncomarkers[PLoS ONE. ]
    Bartlett TE, Olhede SC, Zaikin A. PLoS ONE. 9(1)e84573
  • Suppression of the Interferon and NF-?B Responses by Severe Fever with Thrombocytopenia Syndrome Virus[Journal of Virology. 2012]
    Qu B, Qi X, Wu X, Liang M, Li C, Cardona CJ, Xu W, Tang F, Li Z, Wu B, Powell K, Wegner M, Li D, Xing Z. Journal of Virology. 2012 Aug; 86(16)8388-8401
  • Discovery of Regulatory Elements in Human ATP-Binding Cassette Transporters through Expression Quantitative Trait Mapping[The Pharmacogenomics Journal. 2012]
    Matsson P, Yee SW, Markova S, Morrissey K, Jenkins G, Xuan J, Jorgenson E, Kroetz DL, Giacomini KM. The Pharmacogenomics Journal. 2012 Jun; 12(3)214-226
See all...


  • Gene
    Gene links
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene links
  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...