Anthony Quinn

Commonwealth Scientific and Industrial Research Organisation

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Eli E. Sercarz

La Jolla Institute for Immunology

Penelope G. Shackelford

Washington University in St. Louis

Madeleine W. Cunningham

University of Oklahoma Health Sciences Center

Sarah Rasché

Moffitt Cancer Center

Elisabeth E. Adderson

St. Jude Children's Research Hospital

Kent Jensen

Stanford University

Marcia F. McInerney

University of Toledo

Vipin Kumar

Gurukul Kangri Vishwavidyalaya

W L Carroll

NYU Langone’s Laura and Isaac Perlmutter Cancer Center

Idania Marrero

Inovio Pharmaceuticals (United States)

Cooperative Institutions

University of Toledo

La Jolla Institute for Immunology

Torrey Pines Institute For Molecular Studies

University of California, Los Angeles

Scripps Research Institute

University of Oklahoma Health Sciences Center

Stanford University

University of Toledo Medical Center

Scripps Institution of Oceanography

University of Queensland

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Molecular profile of the T cell receptors of regulatory and effector CD4+ T cells recognizing overlapping determinants on glutamic acid decarboxylase (524–543)

Molecular Immunology (2003)

Jin S. Im Anthony Quinn Eli E. Sercarz Douglas F. Lake

NOD mice

10.1016/j.molimm.2003.09.007

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Citations (7)

Insulin-dependent diabetes loci Idd5 and Idd9 increase sensitivity to experimental autoimmune encephalomyelitis

Clinical Immunology (2005)

Stella Mayo William Köhler Vipin Kumar Anthony Quinn

Congenic

NOD mice

Insulitis

10.1016/j.clim.2005.10.006

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Citations (11)

Report From the 1st International NOD Mouse T-Cell Workshop and the Follow-Up Mini-Workshop

Diabetes (2001)

Daniel L. Kaufman Roland Tisch Nora Sarvetnick Lucienne Chatenoud Leonard C. Harrison

A workshop on autoreactive T-cell responses in NOD mice was held to optimize autoreactive T-cell detection methodologies. Using different proliferation assay protocols, 1 of the 11 participating laboratories detected spontaneous T-cell responses to GAD(524-543) and insulin(9-23) in their NOD mice. Two other laboratories were able to detect autoreactive responses when using enzyme-linked immunospot assay (ELISPOT) and enzyme-linked immunosorbent assay (ELISA) analysis of cytokines in culture supernatants, suggesting that these assays provided greater sensitivity. To address the divergent findings, a follow-up mini-workshop tested NOD mice from four different colonies side-by-side for T-cell proliferative responses to an expanded panel of autoantigens, using the protocol that had enabled detection of responses in the 1st International NOD Mouse T-Cell Workshop. Under these assay conditions, 16 of 16 NOD mice displayed proliferative responses to whole GAD65, 13 of 16 to GAD(524-543), 9 of 16 to GAD(217-236), 7 of 16 to insulin(9-23), and 5 of 16 to HSP277. Thus, spontaneous proliferative T-cell responses can be consistently detected to some β-cell autoantigens and peptides thereof. Overall, the results suggest that more sensitive assays (e.g., ELISPOT, ELISA analysis of cytokines in supernatants, or tetramer staining) may be preferred for the detection of autoreactive T-cells.

ELISPOT

NOD mice

10.2337/diabetes.50.11.2459

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Citations (31)

Development of a Bioconjugate Platform for Modifying the Immune Response of Autoreactive Cytotoxic T Lymphocytes Involved in Type 1 Diabetes

Bioconjugate Chemistry (2019)

Neha Nandedkar-Kulkarni Abhishek Vartak Steven J. Sucheck Katherine A. Wall Anthony Quinn

Type 1 diabetes (T1D) is an autoimmune disorder characterized by autoimmune cell mediated destruction of pancreatic beta cells. Pancreatic beta cells are the only source of insulin in the body. T1D patients then have to depend on insulin injections for their lifetime. Insulin injection can modulate the blood sugar levels, but insulin has little effect on the autoimmune process. Altered peptide ligands (APL) derived from known autoantigens in T1D are able to induce tolerance in autoreactive cells in T1D animal models, but are currently unable to elicit this protection in humans. There is a need to improve immunogenicity of the APLs, as these short peptides can be easily degraded by enzymes in the blood. GAD546–554 is a dominant epitope recognized by autoreactive T cells in the nonobese diabetic (NOD) mouse model that can cause destruction of beta cells. Alanine substitution at the eighth position of GAD546–554 peptide (APL9) induced tolerance in a GAD546–554 specific cytotoxic T lymphocyte clone. To improve the antigen presentation and endosomal escape of APL9, we developed a bioconjugate platform that consists of a liposome containing a bioconjugate of APL9 and toll-like receptor 2 ligand Pam3CysSK4 as well as an antibody against macrophage protein F4/80. APL9 bioconjugate liposome with F4/80 antibody was able to induce tolerance in a GAD 546–554 specific clone. Diabetic NOD splenocytes pretreated with APL9 bioconjugate were also not able to transfer diabetes into prediabetic NOD recipient mice. This work is beneficial to prevent T1D as an immunotherapy strategy to render autoreactive immune cells more tolerant of beta cells.

NOD mice

10.1021/acs.bioconjchem.9b00332

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Citations (7)

Antigen-induced T1D in NOD mice

Journal of Autoimmunity (2003)

Anthony Quinn

NOD mice

10.1016/s0896-8411(03)00028-3

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Citations (5)

Interactions of Effectors and Regulators Are Decisive in the Manifestations of Type 1 Diabetes in Nonobese Diabetic Mice

KARGER eBooks (2001)

Anthony Quinn Vipin Kumar Kent Jensen Eli E. Sercarz

10.1159/000060537

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Citations (5)

A novel aza-anthrapyrazole modulates the development of CD4+ effector T cells (P5207)

The Journal of Immunology (2013)

Matthew Clark Miles P. Hacker Anthony Quinn

Abstract BBR3378 is a novel aza-anthrapyrazole that antagonizes autoimmunity and the progression of MOG-induced EAE without the complications noted with anthracycline-based (mitoxantrone) therapy in EAE and human multiple sclerosis. Mitoxantrone induces cell death in rapidly proliferating cells and significant lymphopenia in vivo; however, while most splenic CD4+ cells take up BBR3378 in vivo, only a few are deleted. Moreover, increased dosages of BBR3378 were associated with improved therapeutic impact without concomitant increases in lymphopenia. To determine if BBR3378-mediates regulation of EAE via lymphocyte deletion, splenic T cells were stimulated with anti-CD3 in the presence of low-dose BBR3378 or mitoxantrone. The CD3 blasts showed increased expression of CD25 and CD69, but the enhanced CD4 expression (CD4hi) typically associated with Th progressison to “effector” status was blocked on BBR3378 and mitoxantrone-treated cells, leading to enrichment of slowly proliferating CD4lo-CD69hi T cells. Cytokine production was confined to CD4hi-CD69hi blasts; however, in contrast to mitoxantrone, IL-17 and IFN-gamma production were significantly reduced in the BBR3378-treated cells in the absence of Th cell death. These findings suggest that BBR3378 can regulate specific genes in viable Th cells while impeding the progression of naïve Th cells to full effector status. The Th subsets associated with the induction of EAE were particularly sensitive to BBR3378-mediated suppression.

Mitoxantrone

10.4049/jimmunol.190.supp.68.31

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Citations (0)

972 PLACENTAL TRANSFER OF ANTIBODY: CORRELATION WITH SUBCLASS COMPOSITION

Pediatric Research (1985)

M. Einhorn Anthony Quinn Penelope G. Shackelford

Toxoid

Subclass

10.1203/00006450-198504000-01002

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Citations (2)

Immunoglobulin Variable Region Gene Expression in Response to Haemophilus influenzae Type b Polysaccharide

The Journal of Infectious Diseases (1992)

W L Carroll Elisabeth E. Adderson Anthony Quinn Penelope G. Shackelford

The mechanism(s) responsible for the ontogenic patterns of acquisition of the antibody repertoire is unknown. The immune response to Haemophilus influenzae type b(Rib)capsular polysaccharide provides an excellent model system in which to examine the ontogeny of immunoglobulin variable region expression. A panel of hybridomas secreting human antibodies specific for Rib capsular polysaccharide was developed using peripheral blood lymphocytes from donors immunized with Rib vaccines. Nucleotide sequence analysis of the heavy chain V regions expressed by four of these hybridomas suggests selective use of members of the VHIII gene family in combination with different D and J segments. The nucleotide sequences were highly homologous to two candidate germline gene sequences. Others have reported that these particular germline sequences are expressed in fetal liver, suggesting that the inability of young children to produce antibody to the Rib capsular polysaccharide is not due to failure to express these VH regions early in ontogeny.

Immunoglobulin heavy chain

10.1093/infdis/165-supplement_1-s57

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Citations (7)

Immunoglobulin light chain variable region gene sequences for human antibodies to Haemophilus influenzae type b capsular polysaccharide are dominated by a limited number of V kappa and V lambda segments and VJ combinations.

Journal of Clinical Investigation (1992)

Elisabeth E. Adderson Penelope G. Shackelford Richard A. Insel Anthony Quinn Patricia Wilson

The immune repertoire to Haemophilus influenzae type b capsular polysaccharide (Hib PS) appears to be dominated by certain light chain variable region genes (IgVL). In order to examine the molecular basis underlying light chain bias, IgVL genes have been cloned from a panel of heterohybridomas secreting human anti-Hib PS (antibody) (anti-Hib PS Ab). One hybridoma, representative of the predominant serum clonotype of anti-Hib PS Ab in older children and adults following immunization or Hib infection, uses a V kappa II segment identical to the germline gene A2, and a JK3 segment. A second kappa hybridoma uses a member of the V kappa I family and a JK4 segment. Four lambda antibodies, all cross-reactive with the structurally related antigen Escherichia coli K100 PS, use V lambda VII segments which are 96-98% homologous to one another, and may originate from a single germline gene. Two additional lambda antibodies, not K100-cross-reactive, are encoded by members of the V lambda II family. All lambda antibodies use highly homologous J lambda 2 or J lambda 3 segments. The VJ joints of all lambda antibodies and the V kappa II-encoded antibody are notable for the presence of an arginine codon, suggesting an important role in antigen binding. Although more complex than heavy chain variable region gene usage, a significant portion of serum anti-Hib PS Ab is likely to be encoded by a limited number of V kappa and V lambda segments and VJ combinations, which may be selectively expressed during development, or following antigen exposure.

Kappa

Gene rearrangement

10.1172/jci115649

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Citations (67)