Structural Basis of Chronic Beryllium Disease: Linking Allergic Hypersensitivity and Autoimmunity

Clayton, Gina M.; Wang, Yang; Crawford, Frances; Novikov, Andrey; Wimberly, Brian T.; Kieft, Jeffrey S.; Falta, Michael T.; Bowerman, Natalie A.; Marrack, Philippa; Fontenot, Andrew P.; Dai, Shaodong; Kappler, John W.

doi:10.1016/j.cell.2014.04.048

Cited by 103 publications

(155 citation statements)

References 59 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…We showed that the Be 2+ ion was buried in the acidic pocket between MHC and self-peptides (Clayton et al ., 2014), which limits the alleles of Be 2+ presenting MHC molecules. In contrast, Ni 2+ presentation is far more promiscuous, since Ni 2+ ions are coordinated on top of MHC molecules and self-peptides (Yin et al ., 2012).…”

Section: Discussionmentioning

confidence: 99%

Using DR52c/Ni2+ mimotope tetramers to detect Ni2+ reactive CD4+ T cells in patients with joint replacement failure

Zhang

Wang

Anderson

et al. 2017

Toxicology and Applied Pharmacology

Self Cite

View full text Add to dashboard Cite

T cell mediated hypersensitivity to nickel (Ni2+) is one of the most common causes of allergic contact dermatitis. Ni2+ sensitization may also contribute to the failure of Ni2+ containing joint implants, and revision to non-Ni2+ containing hardware can be costly and debilitating. Previously, we identified Ni2+ mimotope peptides, which are reactive to a CD4+ T cell clone, ANi2.3 (Vα1, Vβ17), isolated from a Ni2+ hypersensitive patient with contact dermatitis. This T cell is restricted to major histocompatibility complex class II (MHCII) molecule, Human Leukocyte Antigen (HLA)-DR52c (DRA, DRB3*0301). However, it is not known if Ni2+ induced T cell responses in sensitized joint replacement failure patients are similar to subjects with Ni2+ induced contact dermatitis. Here, we generated DR52c/Ni2+ mimotope tetramers, and used them to test if the same Ni2+ T cell activation mechanism could be generalized to Ni2+ sensitized patients with associated joint implant failure. We confirmed the specificity of these tetramers by staining of ANi2.3 T cell transfectomas. The DR52c/Ni2+ mimotope tetramer detected Ni2+ reactive CD4+ T cells in the peripheral blood mononuclear cells (PBMC) of patients identified as Ni2+ sensitized by patch testing and/or a positive Ni2+ LPT. When HLA-typed by a DR52 specific antibody, three out of four patients were DR52 positive. In one patient, Ni2+ stimulation induced the expansion of Vβ17 positive CD4+ T cells from 0.8% to 13.3%. We found that the percentage of DR52 positivity and Vβ17 usage in Ni2+ sensitized joint failure patients are similar to Ni sensitized skin allergy patients. Ni2+ independent mimotope tetramers may be a useful tool to identify the Ni2+ reactive CD4+ T cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Using DR52c/Ni2+ mimotope tetramers to detect Ni2+ reactive CD4+ T cells in patients with joint replacement failure

Zhang

Wang

Anderson

et al. 2017

Toxicology and Applied Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Possible candidates include autoantigens (44), or self-antigens modified, for example, by reactive oxygen species generated by UPM (45), or by the structural distortion of the surface of self-peptide MHC complexes, via internal interaction with metallic cations, as has been reported for the HLA-DP2-restricted mechanism of chronic beryllium disease (46). This is of particular interest, because UPM contains a multitude of transition and alkali metals.…”

Section: Discussionmentioning

confidence: 99%

Urban Particulate Matter–Activated Human Dendritic Cells Induce the Expansion of Potent Inflammatory Th1, Th2, and Th17 Effector Cells

Matthews

Pfeffer

Mann

et al. 2016

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Exposure to urban particulate matter (UPM) exacerbates asthmatic lung inflammation. Lung dendritic cells (DCs) are critical for stimulating T cell immunity and in maintaining airway tolerance, but they also react to airway UPM. The adjuvant role of UPM in enhancing primary immune responses by naive cells to allergen has been reported, but the direct effects of UPM-activated DCs on the functionality of human memory CD4 T cells (Tms), which constitute the majority of T cells in the lung, has not been investigated. Blood CD1c 1 DCs were purified and activated with UPM in the presence or absence of house dust mite or tetanus toxoid control antigen. 5-(and -6)-Carboxyfluorescein diacetate succinimidyl ester-labeled blood Tms were cocultured with autologous DCs, T cell proliferation and effector function were assessed using flow cytometry, and secreted cytokines were measured by combined bead array. UPM-DCs elicited IFN-g and IL-13 secretion and induced proliferation in Tms isolated from both allergic patients with asthma and healthy control subjects, whereas only IL-13 was produced by Tms from patients with atopic asthma stimulated by house dust mite-loaded DCs. UPM-DCs drove the expansion and differentiation of a mixed population of Th1, Th2, and Th17 cell effectors through a mechanism that was dependent on major histocompatibility class II but not on cytokine-driven expansion. The data suggest that UPM not only has adjuvant properties but is also a source of antigen that stimulates the generation of Th2, Th1, and Th17 effector phenotypes, which have been implicated in both exacerbations of asthma and chronic inflammatory diseases.

show abstract

“…Recently, the structural basis of chronic beryllium disease has been elucidated (98). This disease is associated with HLA-DP2, where the Be 2+ ion was buried within the Ag-binding cleft and made contacts with the peptide.…”

Section: Aberrant Tcr Reactivitymentioning

confidence: 99%

T Cell Antigen Receptor Recognition of Antigen-Presenting Molecules

Rossjohn

Gras

Miles

et al. 2015

Annu. Rev. Immunol.

616

675

View full text Add to dashboard Cite

The Major Histocompatibility Complex (MHC) locus encodes classical MHC class I and MHC class II molecules and nonclassical MHC-I molecules. The architecture of these molecules is ideally suited to capture and present an array of peptide antigens (Ags). In addition, the CD1 family members and MR1 are MHC class I-like molecules that bind lipid-based Ags and vitamin B precursors, respectively. These Ag-bound molecules are subsequently recognized by T cell antigen receptors (TCRs) expressed on the surface of T lymphocytes. Structural and associated functional studies have been highly informative in providing insight into these interactions, which are crucial to immunity, and how they can lead to aberrant T cell reactivity. Investigators have determined over thirty unique TCR-peptide-MHC-I complex structures and twenty unique TCR-peptide-MHC-II complex structures. These investigations have shown a broad consensus in docking geometry and provided insight into MHC restriction. Structural studies on TCR-mediated recognition of lipid and metabolite Ags have been mostly confined to TCRs from innate-like natural killer T cells and mucosal-associated invariant T cells, respectively. These studies revealed clear differences between TCR-lipid-CD1, TCR-metabolite-MR1, and TCR-peptide-MHC recognition. Accordingly, TCRs show remarkable structural and biological versatility in engaging different classes of Ag that are presented by polymorphic and monomorphic Ag-presenting molecules of the immune system.

show abstract

Structural Basis of Chronic Beryllium Disease: Linking Allergic Hypersensitivity and Autoimmunity

Cited by 103 publications

References 59 publications

Using DR52c/Ni2+ mimotope tetramers to detect Ni2+ reactive CD4+ T cells in patients with joint replacement failure

Using DR52c/Ni2+ mimotope tetramers to detect Ni2+ reactive CD4+ T cells in patients with joint replacement failure

Urban Particulate Matter–Activated Human Dendritic Cells Induce the Expansion of Potent Inflammatory Th1, Th2, and Th17 Effector Cells

T Cell Antigen Receptor Recognition of Antigen-Presenting Molecules

Contact Info

Product

Resources

About