CD4+ T-cell activation for immunotherapy of malignancies using Ii-Key/MHC class II epitope hybrid vaccines

Vaccine ◽  
2012 ◽  
Vol 30 (18) ◽  
pp. 2805-2810 ◽  
Author(s):  
Minzhen Xu ◽  
Nikoletta L. Kallinteris ◽  
Eric von Hofe
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
T Cell Activation ◽  
Cell Activation ◽  
Class Ii ◽  
Cd4 T Cell

scholarly journals H2-M and H2-O as Targeting Vehicles for the MHC Class II Processing Compartment Promote Antigen-Specific CD4+ T Cell Activation

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1053
Author(s):  
Lucia Lapazio ◽  
Monika Braun ◽  
Kaj Grandien
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
T Cell Activation ◽  
Cell Activation ◽  
Class Ii ◽  
Cd4 T Cell ◽  
Antigen Presentation Pathway ◽  
Presentation Pathway ◽  
Class Ii Antigen ◽  
Mhc Class Ii Antigen

CD8 and CD4 T cell activation are both required for a strong and long-lasting T cell immune response. Endogenously expressed proteins are readily processed by the MHC class I antigen presentation pathway, enabling activation of CD8+ T cells. However, the MHC class II antigen presentation pathway, necessary for CD4+ T cell activation, is generally not sufficiently accessible to endogenously expressed proteins, limiting the efficiency of mRNA- or DNA-based vaccines. In the current study, we have evaluated the feasibility of using antigen sequences fused to sequences derived from the H2-M and H2-O proteins, two complexes known to participate in MHC class II antigen processing, for the enhancement of CD4 T-cell activation. We analyzed T cell activation after genetic immunization with mRNA-encoding fusion proteins with the model antigen ovalbumin and sequences derived from H2-M or H2-O. Our results show that H2-M- or H2-O-derived sequences robustly improve antigen-specific CD4 T-cell activation when fused to the antigen of interest and suggest that the approach could be used to improve the efficiency of mRNA- or DNA-based vaccines.

scholarly journals Amino Acid Substitutions in the Putative MHC Class II “Dimer of Dimers” Interface Inhibit CD4+ T Cell Activation

2001 ◽  
Vol 166 (2) ◽  
pp. 800-808 ◽  
Author(s):  
Ragnar Lindstedt ◽  
Nicola Monk ◽  
Giovanna Lombardi ◽  
Robert Lechler
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Mhc Class Ii ◽  
T Cell Activation ◽  
Cell Activation ◽  
Class Ii ◽  
Cd4 T Cell ◽  
Amino Acid Substitutions

scholarly journals Microglia induce CD4 T lymphocyte final effector function and death.

1996 ◽  
Vol 184 (5) ◽  
pp. 1737-1745 ◽  
Author(s):  
A L Ford ◽  
E Foulcher ◽  
F A Lemckert ◽  
J D Sedgwick
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ex Vivo ◽  
Class Ii ◽  
Cd4 T Cell ◽  
Tissue Macrophage ◽  
T Cell Survival

Microglia, a type of tissue macrophage, are the only cells in the central nervous system (CNS) parenchyma to express some major histocompatibility complex (MHC) class II constitutively or to upregulate expression readily. They are thought to play a role in CD4 T cell activation in autoimmune diseases such as multiple sclerosis, as well as in neurodegenerative conditions, Alzheimer's disease in particular. We show here that highly purified MHC class II+ microglia when tested directly ex vivo do indeed support an effector response by an encephalitogenic myelin basic protein-reactive CD4 T cell line from which production of the proinflammatory cytokines, interferon gamma and tumor necrosis factor, is elicited, but not interleukin (IL)-2 secretion or proliferation. After this interaction, the T cells die by apoptosis. Other nonmicroglial but CNS-associated macrophages isolated in parallel stimulate full T cell activation, including IL-2 production, proliferation, and support T cell survival. Neither CNS-derived population expresses B7.1/B7.2. Resident macrophages that terminate effector T cells in tissues constitute a novel and broadly applicable regulatory measure of particular relevance to processes of self-tolerance against sequestered antigens.

scholarly journals Identification of a CD4+ T cell-stimulating antigen of pathogenic bacteria by expression cloning.

1995 ◽  
Vol 182 (6) ◽  
pp. 1751-1757 ◽  
Author(s):  
S Sanderson ◽  
D J Campbell ◽  
N Shastri
Keyword(s):  
T Cells ◽  
Listeria Monocytogenes ◽  
T Cell ◽  
Mhc Class Ii ◽  
T Cell Activation ◽  
Pathogenic Bacteria ◽  
Genomic Library ◽  
Class Ii ◽  
Cd4 T Cell ◽  
Expression Cloning

Identifying the immunogenic proteins that elicit pathogen-specific T cell responses is key to rational vaccine design. While several approaches have succeeded in identifying major histocompatibility complex (MHC) class I bound peptides that stimulate CD8+ T cells, these approaches have been difficult to extend to peptides presented by MHC class II molecules that stimulate CD4+ T cells. We describe here a novel strategy for identifying CD4+ T cell-stimulating antigen genes. Using Listeria monocytogenes-specific, lacZ-inducible T cells as single-cell probes, we screened a Listeria monocytogenes genomic library as recombinant Escherichia coli that were fed to macrophages. The antigen gene was isolated from the E. coli clone that, when ingested by the macrophages, allowed generation of the appropriate peptide/MHC class II complex and T cell activation. We show that the antigenic peptide is derived from a previously unknown listeria gene product with characteristics of a membrane-bound protein.

scholarly journals Inducible MHC Class II Expression by Mast Cells Supports Effector and Regulatory T Cell Activation

2009 ◽  
Vol 182 (8) ◽  
pp. 4686-4695 ◽  
Author(s):  
Taku Kambayashi ◽  
Eric J. Allenspach ◽  
John T. Chang ◽  
Tao Zou ◽  
Jonathan E. Shoag ◽  
...  
Keyword(s):  
T Cell ◽  
Mast Cells ◽  
Mhc Class Ii ◽  
T Cell Activation ◽  
Regulatory T Cell ◽  
Cell Activation ◽  
Class Ii

scholarly journals Involvement of both major histocompatibility complex class II alpha and beta chains in CD4 function indicates a role for ordered oligomerization in T cell activation.

1995 ◽  
Vol 182 (3) ◽  
pp. 779-787 ◽  
Author(s):  
R König ◽  
X Shen ◽  
R N Germain
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
T Cell Activation ◽  
Cell Activation ◽  
Critical Role ◽  
Class Ii ◽  
Specific Receptor ◽  
Single Class ◽  
Histocompatibility Complex ◽  
Beta 2

CD4 is a membrane glycoprotein on T lymphocytes that binds to the same peptide:major histocompatibility complex (MHC) class II molecule recognized by the antigen-specific receptor (TCR), thereby stabilizing interactions between the TCR and peptide;MHC class II complexes and promoting the localization of the src family tyrosine kinase p56lck into the receptor complex. Previous studies identified a solvent-exposed loop on the class II beta 2 domain necessary for binding to CD4 and for eliciting CD4 coreceptor activity. Here, we demonstrate that a second surface-exposed segment of class II is also critical for CD4 function. This site is in the alpha 2 domain, positioned in single class II heterodimers in such a way that it cannot simultaneously interact with the same CD4 molecule as the beta 2 site. The ability of mutations at either site to diminish CD4 function therefore indicates that specifically organized CD4 and/or MHC class II oligomers play a critical role in coreceptor-dependent T cell activation.

scholarly journals Selective immunosuppression by administration of major histocompatibility complex (MHC) class II-binding peptides. I. Evidence for in vivo MHC blockade preventing T cell activation.

1992 ◽  
Vol 175 (5) ◽  
pp. 1345-1352 ◽  
Author(s):  
J C Guéry ◽  
A Sette ◽  
J Leighton ◽  
A Dragomir ◽  
L Adorini
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
T Cell Activation ◽  
Cell Activation ◽  
Class Ii ◽  
Specific Class ◽  
Binding Peptide

Draining lymph node cells (LNC) from mice immunized with hen egg white lysozyme (HEL) display at their surface antigen-MHC complexes able to stimulate, in the absence of any further antigen addition, HEL peptide-specific, class II-restricted T cell hybridomas. Chloroquine addition to these LNC cultures fails to inhibit antigen presentation, indicating that antigenic complexes of class II molecules and HEL peptides are formed in vivo. MHC class II restriction of antigen presentation by LNC from HEL-primed mice was verified by the use of anti-class II monoclonal antibodies. Coinjection of HEL and the I-Ak-binding peptide HEL 112-129 in mice of H-2k haplotype inhibits the ability of LNC to stimulate I-Ak-restricted, HEL 46-61-specific T cell hybridomas. Similar results are obtained in mice coinjected with the HEL peptides 46-61 and 112-129. Inhibition of T hybridoma activation can also be observed using as antigen-presenting cells irradiated, T cell-depleted LNC from mice coinjected with HEL 46-61 and HEL 112-129, ruling out the possible role of either specific or nonspecific suppressor T cells. Inhibition of T cell proliferation is associated with MHC-specific inhibition of antigen presentation and with occupancy by the competitor of class II binding sites, as measured by activation of peptide-specific T cell hybridomas. These results demonstrate that administration of MHC class II binding peptide competitors selectively inhibits antigen presentation to class II-restricted T cells, indicating competitive blockade of class II molecules in vivo.

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