Phagocytic antigen processing and effects of microbial products on antigen processing and T‐cell responses

Ramachandra, Lakshmi; Chu, Rose S.; Askew, David; Noss, Erika H.; Canaday, David H.; Potter, N. Stevenson; Johnsen, Alyssa; Krieg, Arthur Μ.; Nedrud, John G.; Boom, W. Henry; Harding, Clifford V.

doi:10.1111/j.1600-065x.1999.tb01295.x

Cited by 46 publications

(28 citation statements)

References 187 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Surprisingly, we did not observe BCG and TB10.4 in the same vesicles following co-uptake of the two vaccines (Fig. 7), and it could be speculated that delivery of BCG and TB10.4 into different cellular compartments could result in different Ag/epitope processing [38]. It should be noted that the THP-1 cell line was used and not natural occurring macrophages.…”

mentioning

confidence: 80%

Difference in TB10.4 T‐cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis

et al. 2010

View full text Add to dashboard Cite

Most novel vaccines against infectious diseases are based on recombinant Ag; however, only few studies have compared Ag-specific immune responses induced by natural infection with that induced by the same Ag in a recombinant form. Here, we studied the epitope recognition pattern of the tuberculosis vaccine Ag, TB10.4, in a recombinant form, or when expressed by the pathogen Mycobacterium tuberculosis (M.tb), or by the current anti-tuberculosis vaccine, Mycobacterium bovis BCG. We showed that BCG and M.tb induced a similar CD4 1 T-cell specific TB10.4 epitope-pattern, which differed completely from that induced by recombinant TB10.4. This difference was not due to post-translational modifications of TB10.4 or because TB10.4 is secreted from BCG and M.tb as a complex with Rv0287. In addition, BCG and TB10.4/CAF01 were both taken up by DC and macrophages in vivo, and in vitro uptake experiments revealed that both TB10.4 and BCG were transported to Lamp 1 -compartments. BCG and TB10.4 however, were directed to different types of Lamp 1 -compartments in the same APC, which may lead to different epitope recognition patterns. In conclusion, we show that different vectors can induce completely different recognition of the same protein.Key words: Epitopes . Intracellular localization . Subdominant . T cells . Vaccine uptake IntroductionThe size, shape and nature of a synthetic recombinant vaccine and its target pathogen differ significantly. For instance, bacteria are typically in the range of 0.5-10 mm in diameter, which exceed the size of most viruses by 10 to 100-fold, and protein based adjuvanted vaccines are even smaller. In addition, compared with vaccines based on recombinant proteins and an adjuvant, pathogens are often taken up by different mechanisms by the cells of the immune system [1]. The different uptake mechanisms could lead to different intracellular processing of Ag, giving rise to different epitopes [1]. Furthermore, live pathogens express a wide range of specific lipids 1342and proteins that bind a variety of pattern-recognition receptors on phagocytes and induce signaling through these receptors, whereas recent evidence suggests subunit vaccines more specifically tend to target DC through activation of toll-like receptors [2]. These differences are likely to lead to different responses with regard to the priming of the early immune response [3]. For instance, the main host cell of the intracellular pathogen Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis in humans, is thought to be macrophages [4]; however, although mycobacteria are mainly taken up by macrophages, mycobacteria can infect a wide range of cells including neutrophils, epithelial cells and other cell types [5,6]. On the other hand, viral vaccine vectors have been shown to be ingested largely by immature DC [1], and soluble Ag formulated in cationic adjuvants such as CAF01 or IC31 are also believed to target DC [7,8]. Different types of APC have different mechanisms of Ag uptake, different pH levels in lysosomal co...

show abstract

mentioning

confidence: 80%

Difference in TB10.4 T‐cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis

et al. 2010

View full text Add to dashboard Cite

show abstract

“…It has also been shown that intimate cellular interactions can result in transfer of membrane components from one cell to another (28 -30), raising the possibility that proteins could be transferred from a transmigrating cell to ECs during diapedesis. Once the exogenous proteins are acquired by the ECs, our data reveal that the Ag presentation pathway is both proteasome and TAP1 dependent, similar to several known cross-presentation pathways characterized in professional APCs (4,23,24,(31)(32)(33). It is possible that the acquired proteins are directed to the cytosol where they join the cytoplasmic pool of endogenous Ags for processing.…”

Section: Discussionmentioning

confidence: 80%

Mouse Endothelial Cells Cross-Present Lymphocyte-Derived Antigen on Class I MHC via a TAP1- and Proteasome-Dependent Pathway

Bagai

Valujskikh

Canaday

et al. 2005

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

In vivo studies suggest that vascular endothelial cells (ECs) can acquire and cross-present exogenous Ag on MHC-I but the cellular mechanisms underlying this observation remain unknown. We tested whether primary female mouse aortic ECs could cross-present exogenous male Ag to the T cell hybridoma, MHH, specific for HYUty plus Db. MHC-I-deficient male spleen cells provided a source of male Ag that could not directly stimulate the MHH cells. Addition of male but not female MHC-I-deficient spleen cells to wild-type syngeneic female EC induced MHH stimulation, demonstrating EC cross-presentation. 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. Additional experiments revealed that this EC Ag-processing pathway is both proteasome and TAP1 dependent. These studies demonstrate that cultured murine aortic ECs can process and present MHC-I-restricted Ag derived from a separate, live cell, and they offer insight into the molecular requirements involved in this EC Ag presentation process. Through this pathway, ECs expressing cross-presented peptides can participate in the effector phase of T cell-mediated inflammatory responses such as autoimmunity, anti-tumor immunity, and transplant rejection.

show abstract

“…Studies reviewed in this article support model A. (Reproduced from Ramachandra et al 1999a, with permission from Immunological Reviews. Q Immunological Reviews.)…”

Section: Analysis Of Phagosomes For Proteins Involved In Ag Presentationmentioning

confidence: 99%

Phagocytic processing of antigens for presentation by class II major histocompatibility complex molecules

1999

Self Cite

View full text Add to dashboard Cite

Microbes and other particulate antigens (Ags) are internalized by phagocytosis and then reside in plasma membrane‐derived phagosomes. The contribution of phagosomes to the degradation of Ags has long been appreciated. It has been unclear, however, whether peptides derived from these degraded antigens bind class II major histocompatibility complex (MHC‐II) molecules within phagosomes or within endocytic compartments that receive Ag fragments from phagosomes. Recent experiments have demonstrated that phagosomes containing Ag‐ conjugated latex beads express a full complement of Ag‐processing molecules, e.g. MHC‐II molecules, invariant chain, H2‐DM and proteases sufficient to degrade bead‐ associated Ag. These phagosomes mediate the formation of peptide–MHC‐II complexes, which are transported to the cell surface and presented to T cells. Phagosomes acquire both newly synthesized and plasma membrane‐derived MHC‐II molecules, but the formation of peptide–MHC‐II complexes in phagosomes primarily involves newly synthesized MHC‐II molecules. The content and traffic of phagosomal proteins vary considerably with the type of Ag ingested. Pathogenic microbes can alter phagosome composition and function to reduce Ag processing. For example, Mycobacterium tuberculosis blocks the maturation of phagosomes and reduces the ability of infected cells to present exogenous soluble protein Ags.

show abstract

Phagocytic antigen processing and effects of microbial products on antigen processing and T‐cell responses

Cited by 46 publications

References 187 publications

Difference in TB10.4 T‐cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis

Difference in TB10.4 T‐cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis

Mouse Endothelial Cells Cross-Present Lymphocyte-Derived Antigen on Class I MHC via a TAP1- and Proteasome-Dependent Pathway

Phagocytic processing of antigens for presentation by class II major histocompatibility complex molecules

Contact Info

Product

Resources

About