Immunodominance of H60 Is Caused by an Abnormally High Precursor T Cell Pool Directed against Its Unique Minor Histocompatibility Antigen Peptide

Choi, Eun Young; Christianson, Gregory J.; Yoshimura, Yoshitaka; Sproule, Thomas J.; Jung, Nadja; Joyce, Sebastian; Roopenian, Derry C.

doi:10.1016/s1074-7613(02)00428-4

Cited by 85 publications

(92 citation statements)

References 47 publications

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“…In this regard, in our pH60͞ CEA vaccine, H60 may provide an allogeneic stimulus as well as the stimulation and costimulation of NK and T cells. It is possible that the anti-H60 immune response is so dominant (49) that it overshadows the tumor-specific responses. However, our data indicate that the pH60͞CEA vaccine successfully induced both potent NK-and CEA-specific CTL responses.…”

Section: Discussionmentioning

confidence: 99%

DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor

Zhou

Luo

Lo³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The interaction of NKG2D, a stimulatory receptor expressed on natural killer (NK) cells and activated CD8 ؉ T cells, and its ligands mediates stimulatory and costimulatory signals to these cells. Here, we demonstrate that DNA-based vaccines, encoding syngeneic or allogeneic NKG2D ligands together with tumor antigens such as survivin or carcinoembryonic antigen, markedly activate both innate and adaptive antitumor immunity. Such vaccines result in highly effective, NK؊ and CD8 ؉ T cell-mediated protection against either breast or colon carcinoma cells in prophylactic and therapeutic settings. Notably, this protection was irrespective of the NKG2D ligand expression level of the tumor cells. Hence, this strategy has the potential to lead to widely applicable and possibly clinically useful DNA-based cancer vaccines.NK cells ͉ NKG2D ligands ͉ T cells ͉ survivin ͉ Peyer's patches

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Section: Discussionmentioning

confidence: 99%

DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor

Zhou

Luo

Lo³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…They, the mHAs, have hierarchical immunodominance that also likely contributes to GVHD variability. 13 Furthermore, the impact of mHAs is likely to be expanded further by the process of epitope spreading, which is a process in which the target of an immune response extends from the intended antigen to other epitopes. 14 Damage induced by conditioning regimens and underlying diseases.…”

Section: Triggers For Induction Of Gvhdmentioning

confidence: 99%

New perspectives on the biology of acute GVHD

Paczesny

Hanauer

Sun

et al. 2009

Bone Marrow Transplant

158

126

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The use of allogeneic hematopoietic cell transplantation (HCT) has increased as new techniques have been developed for transplantation in patients who previously would not have been considered HCT candidates. However, its efficacy continued to be limited by the development of frequent and severe acute GVHD. The complex and intricate pathophysiology of acute GVHD is a consequence of interactions between the donor and host innate and adaptive immune responses. Multiple inflammatory molecules and cell types are implicated in the development of GVHD that can be categorized as:(1) triggers that initiate GVHD by therapy-induced tissue damage and the antigen disparities between host and graft tissue; (2) sensors that detect the triggers, that is, process and present alloantigens; (3) mediators such as T-cell subsets (naive, memory, regulatory, Th17 and natural killer T cells) and (4) the effectors and amplifiers that cause damage of the target organs. These multiple inflammatory molecules and cell types that are implicated in the development of GVHD have been described with models that use stepwise cascades. Herein, we provide a novel perspective on the immunobiology of acute GVHD and briefly discuss some of the outstanding questions and limitations of the model systems.

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“…Antigenic peptides from mH-Ags have served as useful models to understand antigen processing and presentation (Spierings et al, 2003;Engelhard et al, 2002;Malarkannan et al, 1999), immunodominance (van Els et al, 1992;Wolpert et al, 1998;Choi et al, 2002), graft rejections (Korngold and Sprent, 1983), GvL (Spierings et al, 2003;Mutis et al, 2002;Riddell et al, 2002;Nishida et al, 2004), and structural analyses of TCR-peptide/MHC interactions (Ostrov et al, 2002). H7 is one of the classical mH-Ag that was originally defined by Snell.…”

Section: Discussionmentioning

confidence: 99%

Recognition of allo-peptide is governed by novel anchor imposition and limited variations in TCR contact residues

Reinbold

Malarkannan

2008

Molecular Immunology

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Immune specificity of a T cell is determined by the TCR contact residues exposed on the antigenic peptide/MHC complex. Naturally processed, biallelic epitopes from H7 minor histocompatibility (mH) antigen vary in position 7 (p7) from aspartic acid (D) to a glutamic acid (E), which differ by an additional methylene (-CH 2 ) in the side chain. Here, we show that this variation generates a strong anti-H7a or anti-H7b cytotoxic T cell responses. Further, the H7 allelic peptides use p6 asparagine as their central anchor residue and amino acid variations in either the canonical p5 or the predicted p6 anchor positions in the antigenic epitope were detrimental for TCR recognition. In addition, introduction of any other amino acids, except asparagine, in the polymorphic p7 significantly abolished the ability of anti-H7b TCR recognition. This demonstrates that only an asparagine with an amine group as a side chain instead of a charged oxygen radical could effectively stimulate the anti-H7b specific T cells. Our findings provide evidence that mH antigenspecific TCRs are highly stringent in recognizing their cognate epitopes.

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Immunodominance of H60 Is Caused by an Abnormally High Precursor T Cell Pool Directed against Its Unique Minor Histocompatibility Antigen Peptide

Cited by 85 publications

References 47 publications

DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor

DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor

New perspectives on the biology of acute GVHD

Recognition of allo-peptide is governed by novel anchor imposition and limited variations in TCR contact residues

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