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  • The American Association of Immunologists  (6)
  • 1
    Online-Ressource
    Online-Ressource
    Allogeneic HLA-A*02–Restricted WT1-Specific T Cells from Mismatched Donors Are Highly Reactive but Show Off-Target Promiscuity
    The American Association of Immunologists ; 2011
    In:  The Journal of Immunology Vol. 187, No. 5 ( 2011-09-01), p. 2824-2833
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 187, No. 5 ( 2011-09-01), p. 2824-2833
    Kurzfassung: T cells recognizing tumor-associated Ags such as Wilms tumor protein (WT1) are thought to exert potent antitumor reactivity. However, no consistent high-avidity T cell responses have been demonstrated in vaccination studies with WT1 as target in cancer immunotherapy. The aim of this study was to investigate the possible role of negative thymic selection on the avidity and specificity of T cells directed against self-antigens. T cell clones directed against the HLA-A*0201–binding WT1126–134 peptide were generated from both HLA-A*02–positive (self-HLA–restricted) and HLA-A*02–negative [nonself (allogeneic) HLA [allo-HLA]-restricted] individuals by direct ex vivo isolation using tetramers or after in vitro priming and selection. The functional avidity and specificity of these T cell clones was analyzed in-depth. Self-HLA–restricted WT1-specific clones only recognized WT1126–134 with low avidities. In contrast, allo-HLA–restricted WT1 clones exhibited profound functional reactivity against a multitude of HLA-A*02–positive targets, even in the absence of exogenously loaded WT1 peptide, indicative of Ag-binding promiscuity. To characterize this potential promiscuity, reactivity of the T cell clones against 400 randomly selected HLA-A*0201–binding peptides was investigated. The self-HLA–restricted WT1-specific T cell clones only recognized the WT1 peptide. In contrast, the allo-HLA–restricted WT1-reactive clones recognized besides WT1 various other HLA-A*0201–binding peptides. In conclusion, allogeneic HLA-A*02–restricted WT1-specific T cells isolated from mismatched donors may be more tumor-reactive than their autologous counterparts but can show specific off-target promiscuity of potential clinical importance. As a result of this, administration of WT1-specific T cells generated from HLA-mismatched donors should be performed with appropriate precautions against potential off-target effects.
    Materialart: Online-Ressource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.1100852
    RVK:
    XA 54100
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: The American Association of Immunologists
    Publikationsdatum: 2011
    ZDB Id: 1475085-5
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 2
    Online-Ressource
    Online-Ressource
    Impact of Peptides on the Recognition of HLA Class I Molecules by Human HLA Antibodies
    The American Association of Immunologists ; 2005
    In:  The Journal of Immunology Vol. 175, No. 9 ( 2005-11-01), p. 5950-5957
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 175, No. 9 ( 2005-11-01), p. 5950-5957
    Kurzfassung: MHC class I molecules expressed on cell surfaces are composed of H chain, β2-microglobulin and any of a vast array of peptides. The role of peptide in the recognition of HLA class I by serum HLA Abs is unknown. In this study, the solid-phase assay of a series (n = 11) of HLA-A2-reactive, pregnancy-induced, human mAbs on a panel (n = 12) of recombinant monomeric HLA-A2 molecules, each containing a single peptide, revealed peptide selectivity of the mAbs. The flow cytometry membrane staining intensities on the HLA-A2-transduced cell line K562, caused by these mAbs, correlated with the number of monomer species detected by the mAbs. Flow cytometry staining on HLA-A2-bearing cell lines of a variety of lineages was indicative of tissue selectivity of these HLA-A2 mAbs. This tissue selectivity suggests that the deleterious effect on allografts is confined to alloantibodies recognizing only HLA class I loaded with peptides that are derived from tissue-specific and household proteins. Since Abs that are only reactive with HLA loaded with irrelevant peptides are expected to be harmless toward allografts, the practice of HLA Ab determination on lymphocyte-derived HLA deserves reconsideration.
    Materialart: Online-Ressource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.175.9.5950
    RVK:
    XA 54100
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: The American Association of Immunologists
    Publikationsdatum: 2005
    ZDB Id: 1475085-5
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 3
    Online-Ressource
    Online-Ressource
    Discovery of T Cell Epitopes Implementing HLA-Peptidomics into a Reverse Immunology Approach
    The American Association of Immunologists ; 2013
    In:  The Journal of Immunology Vol. 190, No. 8 ( 2013-04-15), p. 3869-3877
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 190, No. 8 ( 2013-04-15), p. 3869-3877
    Kurzfassung: T cell recognition of minor histocompatibility Ags (MiHA) plays an important role in the graft-versus-tumor effect of allogeneic stem cell transplantation. Selective infusion of T cells reactive for hematopoiesis-restricted MiHA presented in the context of HLA class I or II molecules may help to separate the graft-versus-tumor effects from graft-versus-host disease effects after allogeneic stem cell transplantation. Over the years, increasing numbers of MiHA have been identified by forward immunology approaches, and the relevance of these MiHA has been illustrated by correlation with clinical outcome. As the tissue distribution of MiHA affects the clinical outcome of T cell responses against these Ags, it would be beneficial to identify additional predefined MiHA that are exclusively expressed on hematopoietic cells. Therefore, several reverse immunology approaches have been explored for the prediction of MiHA. Thus far, these approaches frequently resulted in the identification of T cells directed against epitopes that are not naturally processed and presented. In this study we established a method for the identification of biologically relevant MiHA, implementing mass spectrometry–based HLA-peptidomics into a reverse immunology approach. For this purpose, HLA class I binding peptides were eluted from transformed B cells, analyzed by mass spectrometry, and matched with a database dedicated to identifying polymorphic peptides. This process resulted in a set of 40 MiHA candidates that were evaluated in multiple selection steps. The identification of LB-NISCH-1A demonstrated the technical feasibility of our approach. On the basis of these results, we present an approach that can be of value for the efficient identification of MiHA or other T cell epitopes.
    Materialart: Online-Ressource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.1202351
    RVK:
    XA 54100
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: The American Association of Immunologists
    Publikationsdatum: 2013
    ZDB Id: 1475085-5
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 4
    Online-Ressource
    Online-Ressource
    Cutting Edge: Unconventional CD8+ T Cell Recognition of a Naturally Occurring HLA-A*02:01–Restricted 20mer Epitope
    The American Association of Immunologists ; 2022
    In:  The Journal of Immunology Vol. 208, No. 8 ( 2022-04-15), p. 1851-1856
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 208, No. 8 ( 2022-04-15), p. 1851-1856
    Kurzfassung: Unconventional HLA class I–restricted CD8+ T cell epitopes, longer than 10 aa, have been implicated to play a role in human immunity against viruses and cancer. T cell recognition of long peptides, centrally bulging from the HLA cleft, has been described previously. Alternatively, long peptides can contain a linear HLA-bound core peptide, with a N- or C-terminal peptide “tail” extending from the HLA peptide binding groove. The role of such a peptide “tail” in CD8+ T cell recognition remains unclear. In this study, we identified a 20mer peptide (FLPTPEELGLLGPPRPQVLA [FLP]) derived from the IL-27R subunit α gene restricted to HLA-A*02:01, for which we solved the crystal structure and demonstrated a long C-terminal “tail” extension. FLP-specific T cell clones demonstrated various recognition modes, some T cells recognized the FLP core peptide, while for other T cells the peptide tail was essential for recognition. These results demonstrate a crucial role for a C-terminal peptide tail in immunogenicity.
    Materialart: Online-Ressource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.2101208
    RVK:
    XA 54100
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: The American Association of Immunologists
    Publikationsdatum: 2022
    ZDB Id: 1475085-5
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 5
    Online-Ressource
    Online-Ressource
    Investigation of Peptide Involvement in T Cell Allorecognition Using Recombinant HLA Class I Multimers
    The American Association of Immunologists ; 2005
    In:  The Journal of Immunology Vol. 175, No. 3 ( 2005-08-01), p. 1706-1714
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 175, No. 3 ( 2005-08-01), p. 1706-1714
    Kurzfassung: Alloreactive T cells are involved in injurious graft rejection and graft-vs-host disease. However, they can also evoke beneficial responses to tumor Ags restricted by foreign MHC molecules. Manipulation of these alloreactivities requires information on the basis of T cell allorecognition. The vigorous T cell response to foreign MHC molecules may arise from peptide-independent recognition of polymorphic residues of foreign MHC molecules or peptide-specific recognition of novel peptides presented by foreign MHC molecules. We investigated CD8+ T cell allorecognition using recombinant HLA class I/peptide complexes. Peptide-specific allorecognition was examined using tetramers of HLA-A*0201 representing five peptides derived from ubiquitously expressed self-proteins that are known to bind endogenously to HLA-A*0201. Distinct subsets of CD8+ T cells specific for each HLA-A*0201/peptide combination were detected within four in vitro-stimulated T cell populations specific for foreign HLA-A*0201. Peptide-independent allorecognition was investigated using artificial Ag-presenting constructs (aAPCs) coated with CD54, CD80, and functional densities of a single HLA-A*0201/peptide combination for four different peptides. None of the four T cell populations specific for foreign HLA-A*0201 were stimulated by the aAPCs, whereas they did produce IFN-γ upon stimulation with cells naturally expressing HLA-A*0201. Thus, aAPCs did not stimulate putative peptide-independent allorestricted T cells. The results show that these alloreactive populations comprise subsets of T cells, each specific for a self-peptide presented by foreign class I molecules, with no evidence of peptide-independent components.
    Materialart: Online-Ressource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.175.3.1706
    RVK:
    XA 54100
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: The American Association of Immunologists
    Publikationsdatum: 2005
    ZDB Id: 1475085-5
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 6
    Online-Ressource
    Online-Ressource
    Immunopeptidome Analysis of HLA-DPB1 Allelic Variants Reveals New Functional Hierarchies
    The American Association of Immunologists ; 2020
    In:  The Journal of Immunology Vol. 204, No. 12 ( 2020-06-15), p. 3273-3282
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 12 ( 2020-06-15), p. 3273-3282
    Kurzfassung: HLA-DP alleles can be classified into functional T cell epitope (TCE) groups. TCE-1 and TCE-2 are clearly defined, but TCE-3 still represents an heterogeneous group. Because polymorphisms in HLA-DP influence the presented peptidome, we investigated whether the composition of peptides binding in HLA-DP may be used to refine the HLA-DP group classification. Peptidomes of human HLA-DP–typed B cell lines were analyzed with mass spectrometry after immunoaffinity chromatography and peptide elution. Gibbs clustering was performed to identify motifs of binding peptides. HLA-DP peptide-binding motifs showed a clear association with the HLA-DP allele-specific sequences of the binding groove. Hierarchical clustering of HLA-DP immunopeptidomes was performed to investigate the similarities and differences in peptidomes of different HLA-DP molecules, and this clustering resulted in the categorization of HLA-DP alleles into 3-DP peptidome clusters (DPC). The peptidomes of HLA-DPB1*09:01, -10:01, and -17:01 (TCE-1 alleles) and HLA-DPB1*04:01, -04:02, and -02:01 (TCE-3 alleles) were separated in two maximal distinct clusters, DPC-1 and DPC-3, respectively, reflecting their previous TCE classification. HLA-DP alleles categorized in DPC-2 shared certain similar peptide-binding motifs with DPC-1 or DPC-3 alleles, but significant differences were observed for other positions. Within DPC-2, divergence between the alleles was observed based on the preference for different peptide residues at position 9. In summary, immunopeptidome analysis was used to unravel functional hierarchies among HLA-DP alleles, providing new molecular insights into HLA-DP classification.
    Materialart: Online-Ressource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.2000192
    RVK:
    XA 54100
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: The American Association of Immunologists
    Publikationsdatum: 2020
    ZDB Id: 1475085-5
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
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