HLA-F and MHC-I Open Conformers Cooperate in a MHC-I Antigen Cross-Presentation Pathway

Peptides that are presented by MHC class I (MHC-I) are processed from two potential sources, as follows: newly synthesized endogenous proteins for direct presentation on the surface of most nucleated cells and exogenous proteins for cross-presentation typically by professional APCs. In this study, we present data that implicate the nonclassical HLA-F and open conformers of MHC-I expressed on activated cells in a pathway for the presentation of exogenous proteins by MHC-I. This pathway is distinguished from the conventional endogenous pathway by its independence from TAP and tapasin and its sensitivity to inhibitors of lysosomal enzymes, and further distinguished by its dependence on MHC-I allotype-specific epitope recognition for Ag uptake. Thus, our data from in vitro experiments collectively support a previously unrecognized model of Ag cross-presentation mediated by HLA-F and MHC-I open conformers on activated lymphocytes and monocytes, which may significantly contribute to the regulation of immune system functions and the immune defense.

[1]  O. Joffre,et al.  Cross-presentation by dendritic cells , 2012, Nature Reviews Immunology.

[2]  Sarah Seifert,et al.  Rab5 is necessary for the biogenesis of the endolysosomal system in vivo , 2012, Nature.

[3]  Sven Burgdorf,et al.  Cross-Presentation: How to Get there – or How to Get the ER , 2012, Front. Immun..

[4]  J. Neefjes,et al.  Towards a systems understanding of MHC class I and MHC class II antigen presentation , 2011, Nature Reviews Immunology.

[5]  C. Szymanski,et al.  Endo-Lysosomal Vesicles Positive for Rab7 and LAMP1 Are Terminal Vesicles for the Transport of Dextran , 2011, PloS one.

[6]  D. Geraghty,et al.  HLA‐F is a surface marker on activated lymphocytes , 2010, European journal of immunology.

[7]  D. Geraghty,et al.  HLA-F Complex without Peptide Binds to MHC Class I Protein in the Open Conformer Form , 2010, The Journal of Immunology.

[8]  C. Yee,et al.  Conditional Superagonist CTL Ligands for the Promotion of Tumor-Specific CTL Responses , 2010, The Journal of Immunology.

[9]  James McCluskey,et al.  The peptide length specificity of some HLA class I alleles is very broad and includes peptides of up to 25 amino acids in length. , 2009, Molecular immunology.

[10]  Jacopo Meldolesi,et al.  Shedding microvesicles: artefacts no more. , 2009, Trends in cell biology.

[11]  P. Lindner,et al.  Urea-Mediated Cross-Presentation of Soluble Epstein-Barr Virus BZLF1 Protein , 2008, PLoS pathogens.

[12]  P. Cresswell,et al.  Regulation of MHC class I assembly and peptide binding. , 2008, Annual review of cell and developmental biology.

[13]  W. Jefferies,et al.  MHC Class I Endosomal and Lysosomal Trafficking Coincides with Exogenous Antigen Loading in Dendritic Cells , 2008, PloS one.

[14]  Syed M. Rizvi,et al.  MHC class I assembly: out and about. , 2008, Trends in immunology.

[15]  Hidde L. Ploegh,et al.  The known unknowns of antigen processing and presentation , 2008, Nature Reviews Immunology.

[16]  M. Hulett,et al.  Bystander B cells rapidly acquire antigen receptors from activated B cells by membrane transfer , 2008, Proceedings of the National Academy of Sciences.

[17]  G. Randolph,et al.  Antigen presentation by monocytes and monocyte-derived cells. , 2008, Current opinion in immunology.

[18]  John Sidney,et al.  Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection , 2007, Nature Medicine.

[19]  J. Gauldie,et al.  Antigen Presentation by Exosomes Released from Peptide-Pulsed Dendritic Cells Is not Suppressed by the Presence of Active CTL1 , 2007, The Journal of Immunology.

[20]  Mark Yeager,et al.  Gap junction channel structure in the early 21st century: facts and fantasies. , 2007, Current opinion in cell biology.

[21]  Simon C Watkins,et al.  An Intracellular Serpin Regulates Necrosis by Inhibiting the Induction and Sequelae of Lysosomal Injury , 2007, Cell.

[22]  N. Hogg,et al.  CD8+ Dendritic Cells Use LFA-1 to Capture MHC-Peptide Complexes from Exosomes In Vivo1 , 2007, The Journal of Immunology.

[23]  S. Basta,et al.  The Cross‐priming Pathway: A Portrait of an Intricate Immune System , 2007, Scandinavian journal of immunology.

[24]  S. Powis,et al.  Open conformers: the hidden face of MHC-I molecules. , 2007, Trends in immunology.

[25]  E. Trombetta,et al.  Cross-talk between the endocytic pathway and the endoplasmic reticulum in cross-presentation by MHC class I molecules. , 2007, Current opinion in immunology.

[26]  Hidde L. Ploegh,et al.  Antigen Presentation and the Ubiquitin‐Proteasome System in Host–Pathogen Interactions , 2006, Advances in Immunology.

[27]  Kouhei Tsumoto,et al.  Structural basis for recognition of the nonclassical MHC molecule HLA-G by the leukocyte Ig-like receptor B2 (LILRB2/LIR2/ILT4/CD85d) , 2006, Proceedings of the National Academy of Sciences.

[28]  L. Zitvogel,et al.  Prospects for exosomes in immunotherapy of cancer , 2006, Journal of cellular and molecular medicine.

[29]  K. Rock,et al.  Priming of T cells by exogenous antigen cross-presented on MHC class I molecules. , 2006, Current opinion in immunology.

[30]  Eric O Long,et al.  Activation of NK Cells by an Endocytosed Receptor for Soluble HLA-G , 2005, PLoS biology.

[31]  J. Yewdell,et al.  Understanding presentation of viral antigens to CD8+ T cells in vivo: the key to rational vaccine design. , 2005, Annual review of immunology.

[32]  S. Riddell,et al.  Immune evasion proteins of human cytomegalovirus do not prevent a diverse CD8+ cytotoxic T-cell response in natural infection. , 2004, Blood.

[33]  P. Cresswell,et al.  Cellular mechanisms governing cross-presentation of exogenous antigens , 2004, Nature Immunology.

[34]  H. Kiem,et al.  Efficient marking of murine long-term repopulating stem cells targeting unseparated marrow cells at low lentiviral vector particle concentration. , 2004, Molecular therapy : the journal of the American Society of Gene Therapy.

[35]  T. Neff,et al.  Efficient lentiviral gene transfer to canine repopulating cells using an overnight transduction protocol. , 2004, Blood.

[36]  P. Guermonprez,et al.  Pathways for antigen cross presentation , 2004, Springer Seminars in Immunopathology.

[37]  D. Geraghty,et al.  HLA-F Surface Expression on B Cell and Monocyte Cell Lines Is Partially Independent from Tapasin and Completely Independent from TAP1 , 2003, The Journal of Immunology.

[38]  M. Desjardins,et al.  ER-mediated phagocytosis: a new membrane for new functions , 2003, Nature Reviews Immunology.

[39]  Yao-Tseng Chen,et al.  Cross-Presentation of HLA Class I Epitopes from Exogenous NY-ESO-1 Polypeptides by Nonprofessional APCs 1 , 2003, The Journal of Immunology.

[40]  G. Rimmelzwaan,et al.  Antigen processing for MHC class I restricted presentation of exogenous influenza A virus nucleoprotein by B‐lymphoblastoid cells , 2001, Clinical and experimental immunology.

[41]  P. Lehner,et al.  Mobilization of MHC class I molecules from late endosomes to the cell surface following activation of CD34-derived human Langerhans cells , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[42]  C. Melief,et al.  Antigen Loading of MHC Class I Molecules in the Endocytic Tract , 2001, Traffic.

[43]  A. Hubbard,et al.  Isolation of Rat Hepatocyte Plasma Membrane Sheets and Plasma Membrane Domains , 1999, Current protocols in cell biology.

[44]  B. Deurs,et al.  Rab7: a key to lysosome biogenesis. , 2000, Molecular biology of the cell.

[45]  P. A. Biro,et al.  HLA-F Is a Predominantly Empty, Intracellular, TAP-Associated MHC Class Ib Protein with a Restricted Expression Pattern1 , 2000, The Journal of Immunology.

[46]  J. Neefjes,et al.  Recycling MHC class I molecules and endosomal peptide loading. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[47]  M. Davis,et al.  Isolation of high avidity melanoma-reactive CTL from heterogeneous populations using peptide-MHC tetramers. , 1999, Journal of immunology.

[48]  S. Riddell,et al.  In vivo migration and function of transferred HIV-1-specific cytotoxic T cells , 1999, Nature Medicine.

[49]  J. Hansen,et al.  Definition of the gene encoding the minor histocompatibility antigen HA-1 and typing for HA-1 from genomic DNA. , 1998, Tissue antigens.

[50]  M. Llano,et al.  HLA‐E‐bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA‐G‐derived nonamer , 1998, European journal of immunology.

[51]  M. Llano,et al.  HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[52]  R. Tampé,et al.  A critical role for tapasin in the assembly and function of multimeric MHC class I-TAP complexes. , 1997, Science.

[53]  A Sette,et al.  Improved induction of melanoma-reactive CTL with peptides from the melanoma antigen gp100 modified at HLA-A*0201-binding residues. , 1996, Journal of immunology.

[54]  K. Rock,et al.  Antigen processing and presentation by the class I major histocompatibility complex. , 1996, Annual review of immunology.

[55]  P. L. Campbell,et al.  EEA1, an Early Endosome-Associated Protein. , 1995, The Journal of Biological Chemistry.

[56]  S. Tonegawa,et al.  TAP1‐independent loading of class I molecules by exogenous viral proteins , 1995, European journal of immunology.

[57]  J. Monaco,et al.  A molecular model of MHC class-I-restricted antigen processing. , 1992, Immunology today.

[58]  C. Watts,et al.  Cycling of cell-surface MHC glycoproteins through primaquine-sensitive intracellular compartments , 1990, Nature.

[59]  O. Majdic,et al.  Activated human T lymphocytes express MHC class I heavy chains not associated with beta 2-microglobulin , 1990, The Journal of experimental medicine.

[60]  S. Riddell,et al.  The use of anti-CD3 and anti-CD28 monoclonal antibodies to clone and expand human antigen-specific T cells. , 1990, Journal of immunological methods.

[61]  R. Brady,et al.  [116] β-Hexosaminidase A from human placenta , 1972 .