Search results for: Victor H. Engelhard

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Patterns of immune-cell infiltration in murine models of melanoma: roles of antigen and tissue site in creating inflamed tumors

Katie M. Leick, Joel Pinczewski, Ileana S. Mauldin, Samuel J. Young, more

Cancer Immunology, Immunotherapy > 2019 > 68 > 7 > 1121-1132

Immune-cell infiltration is associated with improved survival in melanoma. Human melanoma metastases may be grouped into immunotypes representing patterns of immune-cell infiltration: A (sparse), B (perivascular cuffing), and C (diffuse). Immunotypes have not been defined for murine melanomas, but may provide opportunities to understand mechanism-driving immunotype differences. We performed immunohistochemistry...

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31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two

Casey Ager, Matthew Reilley, Courtney Nicholas, Todd Bartkowiak, more

Journal for ImmunoTherapy of Cancer > 2016 > 4 > 1 > 107-221

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Immune responses in a mouse model of vitiligo with spontaneous epidermal de‐ and repigmentation

Jonathan M. Eby, Hee‐Kap Kang, Jared Klarquist, Shilpak Chatterjee, more

Pigment Cell & Melanoma Research > 27 > 6 > 1075 - 1085

To generate a mouse model of spontaneous epidermal depigmentation, parental h3TA2 mice, expressing both a human‐derived, tyrosinase‐reactive T‐cell receptor on T cells and the matching HLA‐A2 transgene, were crossed to keratin 14‐promoter driven, stem cell factor transgenic (K14‐SCF) mice with intra‐epidermal melanocytes. In resulting Vitesse mice, spontaneous skin depigmentation precedes symmetrical...

article

Regulatory T cells and vasectomy

Claudia Rival, Karen Wheeler, Sarah Jeffrey, Hui Qiao, more

Journal of Reproductive Immunology > 2013 > 100 > 1 > 66-75

CD4+ CD25+ regulatory T cells (Tregs) strongly influence the early and late autoimmune responses to meiotic germ cell antigens (MGCA) and the gonadal immunopathology in vasectomized mice. This is supported by the published and recently acquired information presented here. Within 24h of unilateral vasectomy (uni-vx) the ipsilateral epididymis undergoes epithelial cell apoptosis followed by necrosis,...

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Relapse or Eradication of Cancer Is Predicted by Peptide-Major Histocompatibility Complex Affinity

Boris Engels, Victor H. Engelhard, John Sidney, Alessandro Sette, more

Cancer Cell > 2013 > 23 > 4 > 516-526

Cancers often relapse after adoptive therapy, even though specific T cells kill cells from the same cancer efficiently in vitro. We found that tumor eradication by T cells required high affinities of the targeted peptides for major histocompatibility complex (MHC) class I. Affinities of at least 10 nM were required for relapse-free regression. Only high-affinity peptide-MHC interactions led to efficient...

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Structural Basis for the Presentation of Tumor-Associated MHC Class II-Restricted Phosphopeptides to CD4+ T Cells

Yili Li, Florence R. Depontieu, John Sidney, Theresa M. Salay, more

Journal of Molecular Biology > 2010 > 399 > 4 > 596-603

Dysregulated protein phosphorylation is a hallmark of malignant transformation. Transformation can generate major histocompatibility complex (MHC)-bound phosphopeptides that are differentially displayed on tumor cells for specific recognition by T cells. To understand how phosphorylation alters the antigenic identity of self-peptides and how MHC class II molecules present phosphopeptides for CD4 ...

article

Targeting allergen to FcγRI reveals a novel TH2 regulatory pathway linked to thymic stromal lymphopoietin receptor

Kathryn E. Hulse, Amanda J. Reefer, Victor H. Engelhard, James T. Patrie, more

The Journal of Allergy and Clinical Immunology > 2010 > 125 > 1 > 247-256.e8

The molecule H22–Fel d 1, which targets cat allergen to FcγRI on dendritic cells (DCs), has the potential to treat cat allergy because of its T-cell modulatory properties.We sought to investigate whether the T-cell response induced by H22–Fel d 1 is altered in the presence of the T _H 2-promoting cytokine thymic stromal lymphopoietin (TSLP).Studies were performed in subjects with cat allergy...

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Targeting Fel d 1 to FcγRI induces a novel variation of the TH2 response in subjects with cat allergy

Kathryn E. Hulse, Amanda J. Reefer, Victor H. Engelhard, Shama M. Satinover, more

The Journal of Allergy and Clinical Immunology > 2008 > 121 > 3 > 756-762.e4

Induction of CD4 ⁺ T cells that produce IL-10 or IFN-γ is central to the protective effects of conventional allergen immunotherapy.We examined the T-cell modulatory capacity of a fusion protein (H22–Fel d 1) that targets Fel d 1 to the high-affinity IgG receptor (FcγRI) on antigen-presenting cells.Monocyte-derived dendritic cells pulsed with H22–Fel d 1 were analyzed for surface phenotype...

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The contributions of mass spectrometry to understanding of immune recognition by T lymphocytes

Victor H. Engelhard

International Journal of Mass Spectrometry > 2007 > 259 > 1-3 > 32-39

Over the last 15 years, the ability of mass spectrometry to analyze complex peptide mixtures and identify individual species has provided unprecedented insights into the repertoire of peptide antigens displayed by MHC molecules and recognized by T lymphocytes. These include: understanding the peptide binding specificity of MHC molecules; understanding of roles of different intracellular components...

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Post-translational modifications of naturally processed MHC-binding epitopes

Victor H Engelhard, Michelle Altrich-Vanlith, Marina Ostankovitch, Angela L Zarling

Current Opinion in Immunology > 2006 > 18 > 1 > 92-97

A variety of different post-translational modifications of peptides displayed by class I and II MHC molecules have now been described. Some modifications promote the binding of peptides to MHC molecules, and might also influence the ability of the peptide to be produced by antigen processing pathways. In some instances, the antigen processing components themselves are actually responsible for generating...

article

Identification of a shared epitope recognized by melanoma-specific, HLA-A3-restricted cytotoxic T lymphocytes

Kevin T. Hogan, Michael A. Coppola, Christine L. Gatlin, Lee W. Thompson, more

Immunology Letters > 2003 > 90 > 2-3 > 131-135

We previously established a melanoma-reactive cytotoxic T lymphocyte (CTL) line that recognizes multiple epitopes in the context of HLA-A3. To increase the number of peptides available for use in a vaccine for the treatment of melanoma, we identified one of these epitopes, SQNFPGSQK, through a combination of epitope reconstitution experiments and mass spectrometry. The SQNFPGSQK peptide was also found...

article

Insights into antigen processing gained by direct analysis of the naturally processed class I MHC associated peptide repertoire

Victor H. Engelhard, Anthony G. Brickner, Angela L. Zarling

Molecular Immunology > 2002 > 39 > 3-4 > 127-137

MHC class I molecules are responsible for the presentation of antigenic peptides to CD8+ T lymphocytes. Based on their relatively promiscuous binding of peptides, these molecules display information derived from a large fraction of proteins that are made inside the cell. This review describes our characterization of the peptides comprising this repertoire, with particular attention given to their...

article

Tyrosinase Degradation via Two Pathways during Reverse Translocation to the Cytosol

Claudio A. Mosse, Weiting Hsu, Victor H. Engelhard

Biochemical and Biophysical Research Communications > 2001 > 285 > 2 > 313-319

Previous studies established that after inhibition of proteasome activity, tyrosinase could be detected in the cytosol after initial translation in the endoplasmic reticulum (ER), with a molecular weight consistent with that of a full-length, deglycosylated polypeptide. Here we show that most of these molecules are glycosylated, but have been proteolyzed at the carboxyl terminus by a protease that...

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Determination of Intronic Sequences Adjacent to an Exon Using Polymerase Chain Reaction and Genomic DNA Library Constructed by TA Cloning

Yoshiki Akatsuka, Edus H. Warren, Anthony G. Brickner, Victor H. Engelhard, more

Analytical Biochemistry > 2001 > 289 > 2 > 289-292

article

Pseudomonas Exotoxin-Mediated Delivery of Exogenous Antigens to MHC Class I and Class II Processing Pathways

John D. Lippolis, Kimberly S. Denis-Mize, Laurence H. Brinckerhoff, Craig L. Slingluff, more

Cellular Immunology > 2000 > 203 > 2 > 75-83

Peptides associated with class II MHC molecules are normally derived from exogenous proteins, whereas class I MHC molecules normally associate with peptides from endogenous proteins. We have studied the ability of Pseudomonas exotoxin A (PE) fusion proteins to deliver exogenously added antigen for presentation by both MHC class I and class II molecules. A MHC class II-restricted antigen was fused...

article

Melanomas with concordant loss of multiple melanocytic differentiation proteins: immune escape that may be overcome by targeting unique or undefined antigens

Craig L. Slingluff Jr., Teresa A. Colella, Lee Thompson, D. David Graham, more

Cancer Immunology, Immunotherapy > 1999 > 48 > 12 > 661-672

Abstract Melanoma-reactive HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) lines generated invitro lyse autologous and HLA-matched allogeneic melanoma cells and recognize multiple shared peptide antigens from tyrosinase, MART-1, and Pmel17/gp100. However, a subset of melanomas fail to be lysed by these T cells. In the present report, four different HLA-A*0201+ melanoma cell lines not lysed by melanoma-reactive...

article

The HLA-A ^* 0201-Restricted H-Y Antigen Contains a Posttranslationally Modified Cysteine That Significantly Affects T Cell Recognition

Leslie Meadows, Wei Wang, Joke M. M. den Haan, Els Blokland, more

Immunity > 1997 > 6 > 3 > 273-281

A peptide recognized by two cytotoxic T cell clones specific for the human minor histocompatibility antigen H-Y and restricted by HLA-A ^* 0201 was identified. This peptide originates from SMCY, as do two other H-Y epitopes, supporting the importance of this protein as a major source of H-Y determinants in mice and humans. In naturally processed peptides, T cells only recognize posttranslationally...

article

A Listeria monocytogenes Pentapeptide Is Presented to Cytolytic T Lymphocytes by the H2-M3 MHC Class Ib Molecule

Pamela H. Gulden, Philip Fischer, Nicholas E. Sherman, Wei Wang, more

Immunity > 1996 > 5 > 1 > 73-79

Polymorphism of MHC class Ia molecules severely constrains vaccine development against intracellular pathogens. Antigen presentation by MHC class Ib molecules, which are generally conserved between different individuals, may circumvent this obstacle. Herein, we use tandem mass spectrometry to identify a Listeria monocytogenes pentapeptide antigen that is presented to T lymphocytes by the H2-M3 MHC...

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