Differential requirements for CTL generation by novel immunostimulants: APC tropism, use of the TAP-independent processing pathway, and dependency on CD80/CD86 costimulation

Sheikh, Nadeem A.; Attard, George S.; Rooijen, Nico van; Rajananthanan, P; Hariharan, Kandasamy; Yang, Yao-Hsu; Morrow, W. J. W.

doi:10.1016/s0264-410x(03)00314-1

Cited by 11 publications

(3 citation statements)

References 59 publications

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“…In this situation, what seems to influence which pathway is operative is the physical form of the antigen: iron oxide or polystyrene versus PLGA particles. In another example, presentation of OVA formulated differently can be either TAP‐dependent or ‐independent (115). One possible explanation for this difference is suggested by the observation that after internalization, different kinds of particles localize to different vacuoles (116–119).…”

Section: The Vacuolar Pathway Of Cross‐presentationmentioning

confidence: 99%

Cross‐presentation: underlying mechanisms and role in immune surveillance

Rock

Shen

2005

Immunological Reviews

383

350

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It was originally thought that a cell's major histocompatibility complex (MHC) class I molecules presented peptides derived exclusively from proteins synthesized by the cell itself. However, in some circumstances, antigens from the extracellular environment can be presented on MHC class I molecules and stimulate CD8(+) T-cell immunity, a process termed cross-presentation. Cross-presentation was originally discovered as an obscure phenomenon in transplantation immunity. However, it is now clear that it is a major mechanism by which the immune system monitors tissues and phagocytes for the presence of foreign antigen. Cross-presentation is the only pathway by which the immune system can detect and respond to viral infections or mutations that exclusively occur in parenchymal cells rather than in bone marrow-derived antigen-presenting cells (APCs). Professional APCs, such as dendritic cells, are the principal cells endowed with the capacity to cross-present antigens. In this process, the APCs acquire proteins from other tissue cells through endocytic mechanisms, especially phagocytosis or macropinocytosis. The internalized antigen can then be processed through at least two different mechanisms. In one pathway, the antigen is transferred from the phagosome into the cytosol, where it is hydrolyzed by proteasomes into oligopeptides that are then transported by the transporter associated with antigen processing to MHC class I molecules in the endoplasmic reticulum or phagosomes. In a second pathway, the antigen is cleaved into peptides by endosomal proteases, particularly cathepsin S, and bound by class I molecules probably in the endocytic compartment itself. Depending on the nature of the antigen, one or both of these pathways can contribute to cross-presentation in vivo. The outcome of cross-presentation can be either tolerance or immunity. Which of these outcomes occurs is thought to depend on whether antigens are acquired by themselves alone, leading to tolerance, or with immunostimulatory signals, leading to immunity. One source of such signals is from dying cells that release immunostimulatory 'danger' signals that promote the generation of immunity to their cellular antigens. 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.

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Section: The Vacuolar Pathway Of Cross‐presentationmentioning

confidence: 99%

Cross‐presentation: underlying mechanisms and role in immune surveillance

Rock

Shen

2005

Immunological Reviews

383

350

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“…To formulate the protein vaccine for the present research, purified and endotoxin depleted rGRA1 protein was adjuvanted to Provax, which is known to be a strong inducer of Th1 cytokine and antigen-specific CD8 lymphocyte production. Indeed, Provax is prepared by mixing previously known strong adjuvants squalane and pluronic L121 to Tween-80 [32,33,64]. Adjuvants have been reported to increase the immunogenicity of protein vaccines [64].…”

Section: Discussionmentioning

confidence: 99%

“…highlight the complexity of the immune response and the unpredictable relationships among various parameters such as vaccine strategy to be used against toxoplasmosis, protection and cellular immune response elicited by recombinant protein vaccine or parasite strain used to challenge the mice. In order to comprehensively evaluate these variables, the present study compares cellular immune response and protection potency of a recombinant GRA1 protein vaccine adjuvanted with a strong Th1 inducer Provax [32,33], a wild type GRA1 DNA vaccine and a GRA1 DNA vaccine codon-optimized for protein expression in mammalian cells. Codon usage optimization is widely accepted as a means of increasing the level of in vivo antigen expression from DNA vaccines and improving the cellular and humoral immune responses against the expressed antigens from diverse microorganisms [34][35][36][37][38][39][40][41][42][43][44][45][46][47].…”

Section: Introductionmentioning

confidence: 99%

GRA1 protein vaccine confers better immune response compared to codon-optimized GRA1 DNA vaccine

Döşkaya

Kalantari-Dehaghi

Walsh

et al. 2007

Vaccine

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The present study evaluates immunogenicity and protection potency of a codon-optimized GRA1 DNA vaccine, wild type GRA1 DNA vaccine and an adjuvanted recombinant GRA1 protein vaccine candidate in BALB/c mice against lethal toxoplasmosis. Of the three GRA1 vaccines tested, the recombinant GRA1 protein vaccine results reveal significant increase in immune response and prolonged survival against acute toxoplasmosis compared to DNA vaccinations. Immune response and protection conferred by codon-optimized GRA1 DNA vaccine was slightly better than wild type GRA1 DNA vaccine.

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