Disease relevance of H60

• Selective down-regulation of the NKG2D ligand H60 by mouse cytomegalovirus m155 glycoprotein [1].
• In this study we explored the effect of ischemia/reperfusion injury (IRI) on the expression of H60 and RAE-1 (MICA, B homologues) in mice to study the protective effect of Yisheng injection (YS), an herbal preparation developed from traditional Chinese medicine [2].
• IFN-gamma-treated MCA sarcomas with high levels of H60 were resistant to killing by IL-2-activated NK cells [3].
• Finally, H60/TNT-3 was tested for antitumor efficacy in BALB/c and C57BL/6 mice bearing subcutaneous syngeneic carcinomas [4].
• Treatment with the immunosuppressive drug cyclosporine abolished H60-specific T cell expansion and rescued animals from fatal pancytopenia [5].

High impact information on H60

• Here we demonstrate that ectopic expression of the murine NKG2D ligands Rae1beta or H60 in several tumour cell lines results in potent rejection of the tumour cells by syngeneic mice [6].
• After exposure to carcinogens, skin cells expressed Rae-1 and H60, major histocompatibility complex-related molecules structurally resembling human MICA [7].
• Immunodominance of H60 is caused by an abnormally high precursor T cell pool directed against its unique minor histocompatibility antigen peptide [8].
• Ectopic expression of RAE-1 and H60 confers target susceptibility to NK cell attack [9].
• We show that the mouse cytomegalovirus (MCMV) molecule fcr-1 promotes a rapid down-regulation of NKG2D ligands murine UL16-binding protein like transcript (MULT)-1 and H60 from the cell surface [10].

Biological context of H60

• The cDNAs defined a new H locus (termed H60), located on mouse chromosome 10, and encoded a novel protein that contains the naturally processed octapeptide LTFNYRNL (LYL8) presented by the Kb MHC molecule [11].
• Here we show that the magnitude of NKG2D-mediated cytotoxicity is directly proportional to both the levels of H60 and the nature of major histocompatibility complex (MHC) class I molecules expressed on the target cells [12].
• Quantitative analysis of the immune response to mouse non-MHC transplantation antigens in vivo: the H60 histocompatibility antigen dominates over all others [13].
• H60 is a murine minor histocompatibility antigen that binds to NKG2D and activates an effector phenotype in NK and T cells [4].

Anatomical context of H60

• NKG2D-independent suppression of T cell proliferation by H60 and MICA [14].
• Infection of BALB/c 3T3 cells with the Smith strain of MCMV resulted in strong down-regulation of H60, a high affinity ligand for NKG2D, from the surface of virus-infected cells [15].
• 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 [5].
• In the present study, infusion of lymph node (LN) cells from C57BL/6 mice into C.B10-H2(b)/LilMcd (C.B10) recipients that are mismatched at multiple minor histocompatibility Ags, including the immunodominant Ag H60, produced fatal aplastic anemia [5].

Associations of H60 with chemical compounds

• The H60 minor histocompatibility (H) antigen peptide is derived from a glycoprotein that serves as a ligand for the stimulatory NKG2D receptor [8].
• Treatment with the proteasome inhibitors lactacystin or epoxomicin reversed m155 down-regulation of H60 [15].

Physical interactions of H60

• Cutting edge: the minor histocompatibility antigen H60 peptide interacts with both H-2Kb and NKG2D [16].

Regulatory relationships of H60

• Thus, down-regulation of H60 by m155 is a powerful mechanism of inhibiting NKG2D-mediated antiviral function [15].

Other interactions of H60

• Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity [6].
• Responsiveness to H60- and MICA-mediated suppression requires IL-10 and involves a receptor other than NKG2D [14].
• Real-time T-cell profiling identifies H60 as a major minor histocompatibility antigen in murine graft-versus-host disease [17].
• While RAE-1B6 and H60 display relatively high affinities for NKG2D with K(D) in the 20-30 nM range and k(off )in the 0.03s(-1) to 0.06s(-1) range (t(1/2) approximately 10-20s); the RAE-1 delta variant binds with a lower affinity: K(D) of approximately 750 nM [18].
• In contrast, even a higher expression of H60 molecule on the target cells failed to overcome the inhibition mediated by Ly49A/G receptors [12].

Analytical, diagnostic and therapeutic context of H60

• Western blotting and immunohistochemical assays showed that there was absent or faint H60 and RAE-1 expression in sham liver, but they were apparently increased in ischemic liver; however, the expressions were significantly decreased in the presence of YS [2].
• Southern blot analysis revealed that the H60 locus was polymorphic among the BALB and the B6 strains [11].
• Understanding why the H60 peptide is so immunogenic has important implications in tissue transplantation and vaccine design [8].
• These findings show that immunodominance applies to antigenically complex transplantation settings in vivo and that the responses to the H60 minor H Ag dominates in this model [13].
• The resultant fusion protein, named H60/TNT-3, was produced in NS0 cells and determined by ELISA to possess an H60 epitope [4].

References