cross priming


Summary: Class I-restricted activation of CD8-POSITIVE LYMPHOCYTES resulting from ANTIGEN PRESENTATION of exogenous ANTIGENS (cross-presentation). This is in contrast to normal activation of these lymphocytes (direct-priming) which results from presentation of endogenous antigens.

Top Publications

  1. Bedoui S, Prato S, Mintern J, Gebhardt T, Zhan Y, Lew A, et al. Characterization of an immediate splenic precursor of CD8+ dendritic cells capable of inducing antiviral T cell responses. J Immunol. 2009;182:4200-7 pubmed publisher
    ..The enhanced capacity of CD8(-)CD24(+) DC to induce immune responses upon adoptive transfer makes them an attractive novel tool for DC-based immunotherapies. ..
  2. Qu C, Nguyen V, Merad M, Randolph G. MHC class I/peptide transfer between dendritic cells overcomes poor cross-presentation by monocyte-derived APCs that engulf dying cells. J Immunol. 2009;182:3650-9 pubmed publisher
    ..These data reveal a way in which migratory monocyte-derived DCs and other DCs, like lymph node resident DCs, both mediate cross-presentation. ..
  3. Faure F, Mantegazza A, Sadaka C, Sedlik C, Jotereau F, Amigorena S. Long-lasting cross-presentation of tumor antigen in human DC. Eur J Immunol. 2009;39:380-90 pubmed publisher
    ..These results show that the use of long synthetic peptides allows the efficient, long-lasting, presentation of tumor antigens, suggesting that long peptides represent an interesting approach for active anti-tumor vaccination. ..
  4. Hildner K, Edelson B, Purtha W, Diamond M, Matsushita H, Kohyama M, et al. Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science. 2008;322:1097-100 pubmed publisher
    ..Importantly, rejection of highly immunogenic syngeneic tumors was impaired in Batf3-/- mice. These results suggest an important role for CD8alpha+ dendritic cells and cross-presentation in responses to viruses and in tumor rejection. ..
  5. Di Pucchio T, Chatterjee B, Smed Sorensen A, Clayton S, Palazzo A, Montes M, et al. Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I. Nat Immunol. 2008;9:551-7 pubmed publisher
    ..Our data demonstrate that pDCs use 'ready-made' stores of MHC class I to rapidly present exogenous antigen to CD8+ T cells. ..
  6. Wilson N, Villadangos J. Regulation of antigen presentation and cross-presentation in the dendritic cell network: facts, hypothesis, and immunological implications. Adv Immunol. 2005;86:241-305 pubmed
    ..Throughout, we highlight what we consider to be major knowledge gaps in the field and speculate on possible directions for future research. ..
  7. Schulz O, Diebold S, Chen M, Näslund T, Nolte M, Alexopoulou L, et al. Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature. 2005;433:887-92 pubmed
    ..Thus, TLR3 may have evolved to permit cross-priming of CTLs against viruses that do not directly infect dendritic cells...
  8. Dolan B, Gibbs K, Ostrand Rosenberg S. Dendritic cells cross-dressed with peptide MHC class I complexes prime CD8+ T cells. J Immunol. 2006;177:6018-24 pubmed
    ..Thus, cross-dressing may be an important mechanism by which DC prime naive CD8+ T cells and may explain how CD8+ T cells are primed to Ags that are inefficiently cross-presented. ..
  9. Amigorena S. Y in X priming. Nat Immunol. 2003;4:1047-8 pubmed

More Information


  1. Smith T, Tang X, Maricic I, Garcia Z, Fanchiang S, Kumar V. Dendritic cells use endocytic pathway for cross-priming class Ib MHC-restricted CD8alphaalpha+TCRalphabeta+ T cells with regulatory properties. J Immunol. 2009;182:6959-68 pubmed publisher
  2. Segura E, Villadangos J. Antigen presentation by dendritic cells in vivo. Curr Opin Immunol. 2009;21:105-10 pubmed publisher
    ..Understanding the contribution of each DC subset to a physiological immune response is particularly relevant for rational vaccine design. ..
  3. LeibundGut Landmann S, Osorio F, Brown G, Reis E Sousa C. Stimulation of dendritic cells via the dectin-1/Syk pathway allows priming of cytotoxic T-cell responses. Blood. 2008;112:4971-80 pubmed publisher
    ..These data highlight the ability of non-TLR receptors to bridge innate and adaptive immunity and suggest that dectin-1 agonists may constitute useful adjuvants for immunotherapy and vaccination. ..
  4. Burgdorf S, Scholz C, Kautz A, Tampe R, Kurts C. Spatial and mechanistic separation of cross-presentation and endogenous antigen presentation. Nat Immunol. 2008;9:558-66 pubmed publisher
    ..Thus, cross-presentation is spatially and mechanistically separated from endogenous MHC class I-restricted antigen presentation and is biased toward antigens containing microbial molecular patterns...
  5. Lin M, Zhan Y, Villadangos J, Lew A. The cell biology of cross-presentation and the role of dendritic cell subsets. Immunol Cell Biol. 2008;86:353-62 pubmed publisher
    ..Further consideration is given to antigen transfer between DC subsets and differential presentation to naive vs memory T cells. ..
  6. Monu N, Trombetta E. Cross-talk between the endocytic pathway and the endoplasmic reticulum in cross-presentation by MHC class I molecules. Curr Opin Immunol. 2007;19:66-72 pubmed
    ..Understanding the molecular and cellular basis of cross-presentation will illuminate novel aspects of cell physiology and might lead to improved vaccine design. ..
  7. Bertholet S, Goldszmid R, Morrot A, Debrabant A, Afrin F, Collazo Custodio C, et al. Leishmania antigens are presented to CD8+ T cells by a transporter associated with antigen processing-independent pathway in vitro and in vivo. J Immunol. 2006;177:3525-33 pubmed
  8. Norbury C, Basta S, Donohue K, Tscharke D, Princiotta M, Berglund P, et al. CD8+ T cell cross-priming via transfer of proteasome substrates. Science. 2004;304:1318-21 pubmed
    ..We show here that cross-priming is based on the transfer of proteasome substrates rather than peptides. These findings are potentially important for the rational design of vaccines that elicit CD8+ T cell responses. ..
  9. Moron G, Dadaglio G, Leclerc C. New tools for antigen delivery to the MHC class I pathway. Trends Immunol. 2004;25:92-7 pubmed
    ..The understanding of the relevance of each of these mechanisms in CTL activation will help vaccine design to progress more rationally. ..
  10. Shen L, Rock K. Cellular protein is the source of cross-priming antigen in vivo. Proc Natl Acad Sci U S A. 2004;101:3035-40 pubmed
    ..Therefore, cellular proteins, rather than peptides or heat shock protein/peptide complexes, are the major source of antigen that is transferred from antigen-bearing cells and cross-presented in vivo. ..
  11. Hon H, Oran A, Brocker T, Jacob J. B lymphocytes participate in cross-presentation of antigen following gene gun vaccination. J Immunol. 2005;174:5233-42 pubmed
    ..Collectively, these data indicate that broad expression of the immunogen is required for optimal induction of protective acquired immunity. ..
  12. Ackerman A, Cresswell P. Cellular mechanisms governing cross-presentation of exogenous antigens. Nat Immunol. 2004;5:678-84 pubmed
    ..Here we discuss the potential mechanisms involved in loading exogenous antigens onto MHC class I molecules and the implications of this new evidence for the in vivo function of dendritic cells. ..
  13. Heath W, Belz G, Behrens G, Smith C, Forehan S, Parish I, et al. Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens. Immunol Rev. 2004;199:9-26 pubmed
    ..In this review, we examine the molecular basis for cross-presentation, discuss the role of DC subsets, and examine the contribution of this process to immunity, with some emphasis on DNA vaccination. ..
  14. Chen W, Pang K, Masterman K, Kennedy G, Basta S, Dimopoulos N, et al. Reversal in the immunodominance hierarchy in secondary CD8+ T cell responses to influenza A virus: roles for cross-presentation and lysis-independent immunodomination. J Immunol. 2004;173:5021-7 pubmed
    ..We further show that immunodomination of PA(224-233)-specific TCD8+ by nucleoprotein 366-374-specific TCD8+ plays a critical role in the phenomena, and that this is unlikely to be mediated by TCD8+ lysis of APCs or other cells. ..
  15. Burgdorf S, Kurts C. Endocytosis mechanisms and the cell biology of antigen presentation. Curr Opin Immunol. 2008;20:89-95 pubmed publisher
  16. Gasteiger G, Kastenmuller W, Ljapoci R, Sutter G, Drexler I. Cross-priming of cytotoxic T cells dictates antigen requisites for modified vaccinia virus Ankara vector vaccines. J Virol. 2007;81:11925-36 pubmed
    ..Our data are essential for improved MVA vaccine design, as they demonstrate the need for optimal adjustment of the target antigen properties to the intrinsic requirements of the delivering vector system. ..
  17. del Rio M, Rodriguez Barbosa J, Kremmer E, Forster R. CD103- and CD103+ bronchial lymph node dendritic cells are specialized in presenting and cross-presenting innocuous antigen to CD4+ and CD8+ T cells. J Immunol. 2007;178:6861-6 pubmed
    ..Because these cells are largely absent in CCR7(-/-) mice, our findings strongly suggest that brLN CD103(+) DC are lung-derived and that expression of CCR7 is required for their migration from the lung into its draining lymph node. ..
  18. Chung Y, Chang J, Kim B, Lee J, Kim H, Kang C. Anatomic location defines antigen presentation by dendritic cells to T cells in response to intravenous soluble antigens. Eur J Immunol. 2007;37:1453-62 pubmed
    ..Therefore, the antigen-presenting capacity of each distinct DC subset is determined by its anatomic environment in combination with its surface phenotype. ..
  19. Ma X, Serna A, Xu R, Sigal L. The amino acid sequences flanking an antigenic determinant can strongly affect MHC class I cross-presentation without altering direct presentation. J Immunol. 2009;182:4601-7 pubmed publisher
    ..Our studies may have implications for understanding CP in viral infections and possibly for the design of new vaccines. ..
  20. Smyth L, Herrera O, Golshayan D, Lombardi G, Lechler R. A novel pathway of antigen presentation by dendritic and endothelial cells: Implications for allorecognition and infectious diseases. Transplantation. 2006;82:S15-8 pubmed
    ..In this review, we discuss the possible contributions of the semidirect pathway/MHC transfer in infectious disease. ..
  21. Schnorrer P, Behrens G, Wilson N, Pooley J, Smith C, El Sukkari D, et al. The dominant role of CD8+ dendritic cells in cross-presentation is not dictated by antigen capture. Proc Natl Acad Sci U S A. 2006;103:10729-34 pubmed
    ..This conclusion has important implications for the design of vaccination strategies based on antigen targeting to DC. ..
  22. Bontkes H, Ruizendaal J, Schreurs M, Kramer D, Meijer C, Hooijberg E. Antigen gene transfer to human plasmacytoid dendritic cells using recombinant adenovirus and vaccinia virus vectors. Cell Oncol. 2005;27:175-82 pubmed
    ..However, PDC induced specific CTL activation after pulsing with recombinant protein, indicating that PDC can also cross-present antigens released from surrounding infected cells. ..
  23. Shen H, Ackerman A, Cody V, Giodini A, Hinson E, Cresswell P, et al. Enhanced and prolonged cross-presentation following endosomal escape of exogenous antigens encapsulated in biodegradable nanoparticles. Immunology. 2006;117:78-88 pubmed
  24. Keller S, Bauer M, Manolova V, Muntwiler S, Saudan P, Bachmann M. Cutting edge: limited specialization of dendritic cell subsets for MHC class II-associated presentation of viral particles. J Immunol. 2010;184:26-9 pubmed publisher
    ..Thus, the presentation of viral particles to CD4(+) T cells is not restricted to distinct DC subsets, whereas the presentation of viral particles to CD8(+) T cells is limited to CD8(+) DCs. ..
  25. Smyth L, Harker N, Turnbull W, El Doueik H, Klavinskis L, Kioussis D, et al. The relative efficiency of acquisition of MHC:peptide complexes and cross-presentation depends on dendritic cell type. J Immunol. 2008;181:3212-20 pubmed
    ..We conclude from these observations that the relative efficiency of MHC transfer vs cross-presentation differs markedly between different DC subsets. ..
  26. Powell T, Strutt T, Reome J, Hollenbaugh J, Roberts A, Woodland D, et al. Priming with cold-adapted influenza A does not prevent infection but elicits long-lived protection against supralethal challenge with heterosubtypic virus. J Immunol. 2007;178:1030-8 pubmed
    ..Our results suggest that intranasal vaccination with cold-adapted, attenuated live virus has the potential to provide effective emergency protection against emerging influenza strains for several months. ..
  27. Bedoui S, Whitney P, Waithman J, Eidsmo L, Wakim L, Caminschi I, et al. Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells. Nat Immunol. 2009;10:488-95 pubmed publisher
    ..This indicates CD103(+) DCs are the main migratory subtype able to cross-present viral and self antigens, which identifies another level of specialization for skin DCs. ..
  28. Le Bon A, Tough D. Type I interferon as a stimulus for cross-priming. Cytokine Growth Factor Rev. 2008;19:33-40 pubmed
    ..In this review, we focus on the involvement of IFN-alpha/beta in the induction of CD8+ T cell responses by cross-priming. ..
  29. Hotta C, Fujimaki H, Yoshinari M, Nakazawa M, Minami M. The delivery of an antigen from the endocytic compartment into the cytosol for cross-presentation is restricted to early immature dendritic cells. Immunology. 2006;117:97-107 pubmed
    ..These data indicate that only the early immature stage of DC interferes with endosomal maturation, even after uptake of exogenous antigens, and then transports the antigens into the cytosol...
  30. Bevan M. Cross-priming. Nat Immunol. 2006;7:363-5 pubmed
  31. Tewalt E, Maynard J, Walters J, Schell A, Berwin B, Nicchitta C, et al. Redundancy renders the glycoprotein 96 receptor scavenger receptor A dispensable for cross priming in vivo. Immunology. 2008;125:480-91 pubmed publisher
    ..These observations emphasize the requirement to target multiple receptors and antigen-processing pathways during the rational design of vaccines aimed at eliciting protective T(CD8+). ..
  32. Shen L, Rock K. Priming of T cells by exogenous antigen cross-presented on MHC class I molecules. Curr Opin Immunol. 2006;18:85-91 pubmed
    ..This pathway is of considerable interest because it has an important role in the immune surveillance of tissues for pathogens and cancers. ..
  33. Lizee G, Basha G, Tiong J, Julien J, Tian M, Biron K, et al. Control of dendritic cell cross-presentation by the major histocompatibility complex class I cytoplasmic domain. Nat Immunol. 2003;4:1065-73 pubmed
  34. Sancho D, Joffre O, Keller A, Rogers N, Martinez D, Hernanz Falcón P, et al. Identification of a dendritic cell receptor that couples sensing of necrosis to immunity. Nature. 2009;458:899-903 pubmed publisher
    ..Thus, CLEC9A functions as a SYK-coupled C-type lectin receptor to mediate sensing of necrosis by the principal dendritic-cell subset involved in regulating cross-priming to cell-associated antigens. ..
  35. Naik S, Proietto A, Wilson N, Dakic A, Schnorrer P, Fuchsberger M, et al. Cutting edge: generation of splenic CD8+ and CD8- dendritic cell equivalents in Fms-like tyrosine kinase 3 ligand bone marrow cultures. J Immunol. 2005;174:6592-7 pubmed
    ..This culture system allows access to bona fide counterparts of the splenic DC subsets. ..
  36. Palucka A, Ueno H, Connolly J, Kerneis Norvell F, Blanck J, Johnston D, et al. Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity. J Immunother. 2006;29:545-57 pubmed
    ..Thus, the present results justify the design of larger follow-up studies to assess the clinical response to DC vaccines loaded with killed allogeneic tumor cells in patients with metastatic melanoma. ..
  37. Groothuis T, Neefjes J. The many roads to cross-presentation. J Exp Med. 2005;202:1313-8 pubmed
    ..Here, we discuss the evidence for and against the ER-phagosome concept as well as other possible mechanisms of cross-presentation. ..
  38. Villadangos J, Young L. Antigen-presentation properties of plasmacytoid dendritic cells. Immunity. 2008;29:352-61 pubmed publisher
    ..In this review, we examine the evidence for a potential role of pDC in antigen capture, processing, and presentation to T cells at sites of infection and in the lymph nodes. ..
  39. Ackerman A, Giodini A, Cresswell P. A role for the endoplasmic reticulum protein retrotranslocation machinery during crosspresentation by dendritic cells. Immunity. 2006;25:607-17 pubmed
    ..Thus, crosspresentation appears to result from an adaptation of the retrotranslocation mechanisms involved in the degradation of misfolded ER proteins. ..
  40. Allan R, Waithman J, Bedoui S, Jones C, Villadangos J, Zhan Y, et al. Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity. 2006;25:153-62 pubmed
  41. Winau F, Weber S, Sad S, de Diego J, Hoops S, Breiden B, et al. Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis. Immunity. 2006;24:105-17 pubmed
    ..tuberculosis infection. Taken together, we propose the detour pathway to represent a genuine immunological mechanism mediating crosspriming of CD8 T cells in vivo and protection against tuberculosis. ..
  42. Wolkers M, Brouwenstijn N, Bakker A, Toebes M, Schumacher T. Antigen bias in T cell cross-priming. Science. 2004;304:1314-7 pubmed
    ..Such differences in the ability to cross-present antigens should form important considerations in vaccine design. ..
  43. Fujii S, Shimizu K, Hemmi H, Steinman R. Innate Valpha14(+) natural killer T cells mature dendritic cells, leading to strong adaptive immunity. Immunol Rev. 2007;220:183-98 pubmed
    ..These findings help explain tumor protection via alpha-GalCer and urge development of the DC-NKT axis to provide innate and adaptive immunity to human cancers. ..
  44. Villadangos J, Heath W, Carbone F. Outside looking in: the inner workings of the cross-presentation pathway within dendritic cells. Trends Immunol. 2007;28:45-7 pubmed
    ..Two recent papers describe intracellular components tailored to the dendritic cell cross-presentation pathway. ..
  45. Burgdorf S, Lukacs Kornek V, Kurts C. The mannose receptor mediates uptake of soluble but not of cell-associated antigen for cross-presentation. J Immunol. 2006;176:6770-6 pubmed
    ..Uptake of cell-associated OVA was unaffected by MR deficiency, resulting in unchanged activation of OT-I cells. These findings demonstrate that DC use the MR for endocytosis of a particular Ag type intended for cross-presentation. ..
  46. Rock K, Shen L. Cross-presentation: underlying mechanisms and role in immune surveillance. Immunol Rev. 2005;207:166-83 pubmed
    ..In addition to the critical role of cross-presentation in normal immune physiology, this pathway has considerable potential for being exploited for developing subunit vaccines that elicit both CD4(+) and CD8(+) T-cell immunity. ..
  47. Ratzinger G, Baggers J, de Cos M, Yuan J, Dao T, Reagan J, et al. Mature human Langerhans cells derived from CD34+ hematopoietic progenitors stimulate greater cytolytic T lymphocyte activity in the absence of bioactive IL-12p70, by either single peptide presentation or cross-priming, than do dermal-interstitial or . J Immunol. 2004;173:2780-91 pubmed
    ..These findings merit further comparisons in clinical trials designed to determine the physiologic relevance of these distinctions in activity between LCs and other DCs. ..
  48. Singh V, Ji Q, Feigenbaum L, Leighty R, Hurwitz A. Melanoma progression despite infiltration by in vivo-primed TRP-2-specific T cells. J Immunother. 2009;32:129-39 pubmed publisher
    ..Determining the basis for the inability of the tumor microenvironment to sustain effective antitumor responses will be critical for designing newer, more potent antitumor immunotherapies. ..
  49. Pang S, Zhang L, Wang H, Yi Z, Li L, Gao L, et al. CD8(+) T cells specific for beta cells encounter their cognate antigens in the islets of NOD mice. Eur J Immunol. 2009;39:2716-24 pubmed publisher
    ..However, it remains to be determined whether the initiation of insulitis in spontaneous diabetes is the result of a cognate interaction between naive CD8(+) T cells and islet beta cells. ..
  50. Bachem A, Güttler S, Hartung E, Ebstein F, Schaefer M, Tannert A, et al. Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells. J Exp Med. 2010;207:1273-81 pubmed publisher
    ..These data define CD141+ DCs as professional antigen cross-presenting DCs in the human. ..
  51. Demaria S, Ng B, Devitt M, Babb J, Kawashima N, Liebes L, et al. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys. 2004;58:862-70 pubmed
    ..These results demonstrate that the abscopal effect is in part immune mediated and that T cells are required to mediate distant tumor inhibition induced by radiation. ..
  52. Durand V, Mackenzie J, de Leon J, Mesa C, Quesniaux V, Montoya M, et al. Role of lipopolysaccharide in the induction of type I interferon-dependent cross-priming and IL-10 production in mice by meningococcal outer membrane vesicles. Vaccine. 2009;27:1912-22 pubmed publisher
    ..The importance of LPS in the induction of IL-10 and functional cross-priming has implications for NOMV-based vaccine and adjuvant development. ..
  53. Takamura S, Roberts A, Jelley Gibbs D, Wittmer S, Kohlmeier J, Woodland D. The route of priming influences the ability of respiratory virus-specific memory CD8+ T cells to be activated by residual antigen. J Exp Med. 2010;207:1153-60 pubmed publisher
    ..Thus, two independent factors, initial CD8+ T cell priming in the MLN and prolonged presentation of residual antigen in the MLN, are required to maintain large numbers of antigen-specific memory CD8+ T cells in the lung airways. ..