Cutting Edge: The Minor Histocompatibility Antigen H60 Peptide Interacts with Both H-2Kb and NKG2D

Cerwenka, Adelheid; O’Callaghan, Christopher A.; Hamerman, Jessica A.; Yadav, Rajwardhan; Ajayi, Wilfred U.; Roopenian, Derry C.; Joyce, Sebastian; Lanier, Lewis L.

doi:10.4049/jimmunol.168.7.3131

Cited by 28 publications

(22 citation statements)

References 30 publications

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“…In human patients, mismatch of the adhesion molecule CD31 and of H-Y Ags may cause GVH responses, and the effect could even be advantageous when directed against host leukemic cells (15-17). Among the many minor H Ags that differ between B6 and C.B10 mice, H60 is of unique importance because B6 mice carry a null allele and do not express the protein from which the H60 peptide derives (27,28). The H60 glycoprotein is a member of the retinoic acid early inducible gene family and serves as a ligand for the stimulatory NK receptor NKG2D.…”

Section: Discussionmentioning

confidence: 99%

“…Mismatch at minor H Ags can provoke severe immune responses against host cells upon transplantation in clinical settings as well as in experimental models (10,11,(15)(16)(17)(22)(23)(24)(25), In one minor H Ag-mismatched cell transplantation model, the infusion of B6 lymphocytes to C.B10-H2 b /LilMcd (C.B10) recipients caused restricted T cell expansion of specific V␤ subfamilies (24,26) with immunodominant effects against H60 (10,11,22), a minor H Ag that interacts with both H2K b and NKG2D receptors (27,28). Experimental data indicate, though, that an immunodominant epitope for CD8 T cells, such as H60, cannot elicit a response in the absence of CD4 T cells responding to another helper cell epitope (10,11,22).…”

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confidence: 99%

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Minor Antigen H60-Mediated Aplastic Anemia Is Ameliorated by Immunosuppression and the Infusion of Regulatory T Cells

Chen

Ellison

Eckhaus

et al. 2007

The Journal of Immunology

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Human bone marrow (BM) failure mediated by the immune system can be modeled in mice. In the present study, infusion of lymph node (LN) cells from C57BL/6 mice into C.B10-H2b/LilMcd (C.B10) recipients that are mismatched at multiple minor histocompatibility Ags, including the immunodominant Ag H60, produced fatal aplastic anemia. Declining blood counts correlated with marked expansion and activation of CD8 T cells specific for the immunodominant minor histocompatibility Ag H60. Infusion of LN cells from H60-matched donors did not produce BM failure in C.B10 mice, whereas isolated H60-specific CTL were cytotoxic for normal C.B10 BM cells in vitro. Treatment with the immunosuppressive drug cyclosporine abolished H60-specific T cell expansion and rescued animals from fatal pancytopenia. The development of BM failure was associated with a significant increase in activated CD4+CD25+ T cells that did not express intracellular FoxP3, whereas inclusion of normal CD4+CD25+ regulatory T cells in combination with C57BL/6 LN cells aborted H60-specific T cell expansion and prevented BM destruction. Thus, a single minor histocompatibility Ag H60 mismatch can trigger an immune response leading to massive BM destruction. Immunosuppressive drug treatment or enhancement of regulatory T cell function abrogated this pathophysiology and protected animals from the development of BM failure.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Minor Antigen H60-Mediated Aplastic Anemia Is Ameliorated by Immunosuppression and the Infusion of Regulatory T Cells

Chen

Ellison

Eckhaus

et al. 2007

The Journal of Immunology

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“…However, it is well known that NKG2D ligands display a great degree of polymorphism both in mice (46) and humans (47). Thus, to develop a widely applicable cancer vaccine, it should be determined whether an allogeneic NKG2D ligand can also serve as an adjuvant for DNA vaccines.…”

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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“…Although it is still poorly understood why H60 of BALB.B mice dominates over other minor histocompatibility Ags and elicits particularly strong CTL responses in B6 mice (46,48), the reason why H60 functions as a minor histocompatibility Ag is well understood: the gene for H60 (H60a) is transcribed in BALB.B but not in B6 mice (27). When immunized with BALB.B splenocytes, B6 mice generate CTLs that recognize an H60-derived octamer (LTFNYRNL) presented by H2-K b .…”

Section: Discussionmentioning

confidence: 99%

Two Novel NKG2D Ligands of the Mouse H60 Family with Differential Expression Patterns and Binding Affinities to NKG2D

Takada

Yoshida

Kajikawa

et al. 2008

The Journal of Immunology

109

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H60, originally described as a dominant minor histocompatibility Ag, is an MHC class I-like molecule that serves as a ligand for the NKG2D receptor. In the present study, we identified two novel mouse chromosome 10-encoded NKG2D ligands structurally resembling H60. These ligands, which we named H60b and H60c, encode MHC class I-like molecules with two extracellular domains. Whereas H60b has a transmembrane region, H60c is a GPI-anchored protein. Recombinant soluble H60b and H60c proteins bound to NKG2D with affinities typical of cell–cell recognition receptors (Kd = 310 nM for H60b and Kd = 8.7 μM for H60c). Furthermore, expression of H60b or H60c rendered Ba/F3 cells susceptible to lysis by NK cells, thereby establishing H60b and H60c as functional ligands for NKG2D. H60b and H60c transcripts were detected only at low levels in tissues of healthy adult mice. Whereas H60b transcripts were detectable in various tissues, H60c transcripts were detected mainly in the skin. Infection of mouse embryonic fibroblasts with murine cytomegalovirus induced expression of H60b, but not H60c or the previously known H60 gene, indicating that transcriptional activation of the three types of H60 genes is differentially regulated. The present study adds two new members to the current list of NKG2D ligands.

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Cutting Edge: The Minor Histocompatibility Antigen H60 Peptide Interacts with Both H-2Kb and NKG2D

Cited by 28 publications

References 30 publications

Minor Antigen H60-Mediated Aplastic Anemia Is Ameliorated by Immunosuppression and the Infusion of Regulatory T Cells

Minor Antigen H60-Mediated Aplastic Anemia Is Ameliorated by Immunosuppression and the Infusion of Regulatory T Cells

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

Two Novel NKG2D Ligands of the Mouse H60 Family with Differential Expression Patterns and Binding Affinities to NKG2D

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