Disease relevance of Cross-Priming

• alpha v beta3-dependent cross-presentation of matrix metalloproteinase-2 by melanoma cells gives rise to a new tumor antigen [1].
• Thus, classic MHC class I Ag presentation and cross-priming contribute differentially to the induction of CD8(+) CTLs following exposure to vaccinia virus via different routes [2].
• Fusion of OVA sequence (rOVA, containing OVA(230-359) sequence) to Mycobacterium tuberculosis HSP70 greatly enhanced rOVA processing and MHC-I cross-presentation of OVA(257-264):K(b) complexes by B cells [3].
• This method, coupled with fluorometry and fluorescence microscopy, shows that the TAT PTD derived from human immunodeficiency virus type 1 is rapidly taken up by cells but fails to reach their cytosol, except when dendritic cells, which are known to take up circulating antigens for cross-presentation, are used [4].

High impact information on Cross-Priming

• Therefore, once initiated, GVHD is intensified by donor-derived cells, most probably donor APCs cross-priming alloreactive CD8 cells [5].
• Apoptotic cells overexpress vinculin and induce vinculin-specific cytotoxic T-cell cross-priming [6].
• Successful cross-priming requires that the apoptotic cells provide maturation signals to dendritic cells through CD40-CD40 ligand (CD40L) interactions [6].
• Here we show that signalling through CD40 on the antigen-presenting cells can replace the requirement for TH cells, indicating that T-cell 'help', at least for generation of CTLs by cross-priming, is mediated by signalling through CD40 on the antigen-presenting cell [7].
• Finally, we review findings pertaining to the biological mechanisms that enable DCs to present exogenous antigens on their MHC class I molecules, a process known as cross-presentation [8].

Biological context of Cross-Priming

• Control of dendritic cell cross-presentation by the major histocompatibility complex class I cytoplasmic domain [9].
• Moreover, using genetic models that allow only one mode of antigen presentation, we show here that both cross-presentation of P1A by the host antigen-presenting cells, and direct antigen presentation and costimulation by the tumor cells are sufficient to initiate rapid T cell-clonal expansion in the lymphoid organ [10].
• These results support a model in which activation-induced up-regulation of B7 molecules on APC leads to increased CD28 signaling and a commitment to cross-priming of CD4-dependent CTL [11].
• One consistent feature of infection by ALVAC is that these viruses induce apoptosis, and we show cross-presentation of Ag when uninfected DC are cocultured with ALVAC MART-1-infected DC [12].
• Enforced endocytosis of Ag together with the adjuvant effect of Toll-like receptor 9 ligands might be key for the efficient cross-presentation of exogeneous Ag as well as for effective cross-priming of MHC class I restricted CD8 T effector cells [13].

Anatomical context of Cross-Priming

• We also report that transgenic mice expressing H-2K(b) with a tyrosine mutation mount inferior H-2K(b)-restricted cytotoxic T lymphocyte responses against two immunodominant viral epitopes, providing evidence of a crucial function for cross-priming in antiviral immunity [9].
• Syncytia activate macrophages and fusogenic membrane glycoprotein-mediated cell killing very efficiently promotes cross-priming of immature dendritic cells with a model tumor antigen [14].
• It has been proposed that the cross-priming of CTL responses in vivo involves the transfer to host APCs of heat shock protein glycoprotein 96-chaperoned antigenic peptides released from the endoplasmic reticulum (ER) of dying or infected cells [15].
• CD40L interactions were blocked by in vivo treatment with anti-CD40L mAb MR-1, which inhibited germinal center formation and CD8(+) T cell cross-priming against an exogenous model Ag, OVA [16].
• Furthermore, the proliferation of CFSE-labeled OT-1 cells in response to OVA cross-presentation in vivo was normal in CD36(-/-) bone marrow chimeras, also arguing against a necessary role for CD36 in cross-presentation by DC or other APC [17].

Associations of Cross-Priming with chemical compounds

• We suggest that the alphavbeta5 integrin plays a critical role in the trafficking of exogenous antigen by immature DCs in this cross-priming pathway [18].
• Lactacystin treatment of the donor male MHC-I-deficient spleen cells, to inhibit proteasome function, markedly enhanced EC cross-presentation showing that the process is most efficient for intact proteins rather than degraded peptide fragments [19].
• We here describe that cholesterol is essential for cross-presentation of antigens loaded via macropinocytosis into APCs [20].
• B-cell subsets responsive to fluorescein-conjugated antigens. II. "Cross-priming" and its elimination by bromodeoxyuridine and light [21].

Gene context of Cross-Priming

• Instead, it appears that TNF-alpha can promote cross-presentation of islet antigen to CD8(+) T cells using a unique CD40-CD154-independent pathway [22].
• Selective Rac1 inhibition in dendritic cells diminishes apoptotic cell uptake and cross-presentation in vivo [23].
• Coordinated regulation of B7 costimulation and TAP-dependent cross-presentation results in priming of Ag-specific CD8(+) CTL, whereas CD40, B7, and IL-12 costimulation is required for priming of CD4(+) Th cells by ISS-based vaccines [24].
• Our study provides the first genetic evidence for the roles of Hsf1 in regulating cross-presentation of MHC class I-associated Ags [25].
• Viral immunity: cross-priming with the help of TLR3 [26].

Analytical, diagnostic and therapeutic context of Cross-Priming

• This model of conditional cross-presentation establishes an original level of action for IFN-gamma as an effective immune modulator and supports the use of IFN-gamma in protein vaccination strategies targeting LCs [27].
• Cross-priming with heterologous MSP1s was as efficient as homologous immunizations in inducing anti-MSP1 Abs [28].

References