Cross-presentation: a general mechanism for CTL immunity and tolerance
Section snippets
A mechanism for directing peripheral antigen into the MHC class I presentation pathway
Most studies showing exclusion of exogenous antigen from the class I presentation pathway have used the favourite tools of the cellular immunologist, notably, fully activated effector T cells and established tumour-cell lines to present the target antigen3, 4. These reagents mimic the physiological situation where armed and migrating effector CTLs lyse virus-infected target cells, but they do not address the nature of antigen presentation during the priming phase of the immune response. Such
Cross-presentation is involved in CD8+ T-cell deletion
Cross-presentation of exogenous antigen was originally described in the context of T-cell priming, but there is also evidence that a similar presentation mechanism can contribute to T-cell tolerance18, 19. von Boehmer and Hafen[18]showed that maturing CD8+ T cells could be tolerized to minor histocompatibility antigens expressed on thymic epithelial cells, even when such cells did not carry the correct restricting MHC class I elements. In this case the antigen was presented by APCs most likely
CD4+ T-cell involvement can determine the choice between cross-priming and cross-tolerance
Antigen-specific CD4+ Th cells are important contributors to effective CTL priming. It is established that many, although clearly not all, CTL responses require the active involvement of CD4+ T cells25, 26, 27. However, the basis for this requirement has largely remained obscure. The contribution of Th cells to humoral immune responses is elegantly explained by a cognate interaction involving the B-cell-expressed MHC class II molecules and antigen-specific CD4+ T cells, often with the active
Identity of the cross-presenting APC and access to the MHC class I presentation pathway
The identity of the cross-presenting APC and the means by which it can direct the class I-restricted presentation of exogenous antigens remains controversial. In addition, we have little idea where the APCs capture their antigenic cargo: in the tissues where the antigen is expressed or the lymph nodes where the presentation actually takes place.
There are a number of mechanisms which appear to provide exogenous antigens access to the MHC class I-restricted presentation pathway. For example, in
The physiological role for cross-priming
We have purposely focused our discussion on the CTL response to antigens expressed in locations outside the secondary lymphoid organs. In this situation (Fig. 3), the cross-presentation mechanism permits the co-localization of antigen, professional APCs, Th cells and CTLs in a central location, notably the lymph nodes that drain sites of peripheral antigen expression. As Bevan suggested, this pathway may be critical for responses to tissue-tropic viruses[11], but is this the only purpose of
Acknowledgements
The authors wish to thank P. Gleeson and members of the Carbone and Heath laboratories for helpful comments.
References (64)
- et al.
Cell
(1988) Curr. Opin. Immunol.
(1994)Immunol. Today
(1991)- et al.
Cell
(1991) - et al.
Cell
(1991) - et al.
Immunity
(1995) - et al.
Blood
(1997) - et al.
Immunity
(1996) - et al.
Annu. Rev. Immunol.
(1993) - et al.
Annu. Rev. Immunol.
(1996)
Science
J. Exp. Med.
Science
J. Exp. Med.
J. Exp. Med.
Nature
J. Exp. Med.
Eur. J. Immunol.
Proc. Natl. Acad. Sci. U. S. A.
J. Immunol.
Eur. J. Immunol.
J. Exp. Med.
Nature
J. Exp. Med.
Eur. J. Immunol.
Curr. Top. Microbiol. Immunol.
J. Exp. Med.
Ann. New York Acad. Sci.
J. Exp. Med.
Nature
J. Exp. Med.
Cited by (215)
Purification of the subcellular compartment in which exogenous antigens undergo endoplasmic reticulum-associated degradation from dendritic cells
2016, HeliyonCitation Excerpt :Cytotoxic T lymphocytes (CTLs), which destroy these non-self cells by recognizing non-self markers, are derived from naive CD8+ T cells after appropriate stimulation by antigen presenting cells (APCs) harboring both with specific antigen-MHC class I complexes and costimulatory molecules [4, 5]. In APCs, antigens from non-self cells can be internalized and presented on MHC class I molecules [6, 7, 8]. This process is a unique phenomenon among several subsets of dendritic cells (DCs) [9, 10, 11, 12, 13], and is called cross-presentation [6, 7, 8].
Mechanisms of Peptide Vaccination in Mouse Models. Tolerance, Immunity, and Hyperreactivity.
2012, Advances in ImmunologyDNA-mediated vaccination conferring protection against infectious bursal disease in broiler chickens in the presence of maternal antibody
2010, VaccineCitation Excerpt :The other pathway is that DNA is taken up directly by APCs such as dendritic cells or macrophages and the viral antigens are presented by MHC I molecules to activate T cells to become CTL [29,30]. By cross-priming, APCs uptake vaccine antigens produced by somatic cells and can also present the exogenous peptides by MHC I molecule to activate cytotoxic T cells [31–33]. In the presence of Mab, the induction of cellular immunity by DNA vaccination is not inhibited when the DNA is directly taken up by APCs.
Immunotherapy of hepatocellular carcinoma with a vaccine based on xenogeneic homologous α fetoprotein in mice
2008, Biochemical and Biophysical Research CommunicationsThe PI3Kδ inhibitor idelalisib impairs the function of human dendritic cells
2021, Cancer Immunology, ImmunotherapyElotuzumab spares dendritic cell integrity and functionality
2021, Journal of Cancer Research and Clinical Oncology