<scp>HLA‐E</scp> allelic genotype correlates with <scp>HLA‐E</scp> plasma levels and predicts early progression in chronic lymphocytic leukemia

Wagner, Bettina; Nardi, Fabiola da Silva; Schramm, Sabine; Kraemer, Thomas; Celik, Alexander A.; Dürig, Jan; Horn, Peter A.; Dührsen, Ulrich; Nückel, Holger; Rebmann, Vera

doi:10.1002/cncr.30427

Cited by 37 publications

(39 citation statements)

References 57 publications

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“…HLA-Ib molecules are involved in a diverse range of functions in adaptive and innate immunity. In recent years, knowledge about the function (Wagner et al 2017 ; Kraemer et al 2015 ; Celik et al 2018a ) and biophysical features (Celik et al 2018b ; Celik et al 2016 ; Petrie et al 2008 ) of HLA-Ib molecules are engaged in the fundamental understanding of tumor immunosurveillance, pathogen recognition, regulation of autoimmunity and virus-induced immunopathology (Kochan et al 2013 ; Rebmann et al 2014 ; Hofstetter et al 2011 ), their upregulation during pathogenic episodes support the mediation of immune tolerance (Celik et al 2018b ). During viral infection, HLA-E is upregulated on the cell surface and avoids the recognition of infected HLA-Ia empty cells by NK cell (Kraemer et al 2014 ).…”

Section: Introductionmentioning

confidence: 99%

HLA-F*01:01 presents peptides with N-terminal flexibility and a preferred length of 16 residues

et al. 2019

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HLA-F belongs to the non-classical HLA-Ib molecules with a marginal polymorphic nature and tissue-restricted distribution. HLA-F is a ligand of the NK cell receptor KIR3DS1, whose activation initiates an antiviral downstream immune response and lead to delayed disease progression of HIV-1. During the time course of HIV infection, the expression of HLA-F is upregulated while its interaction with KIR3DS1 is diminished. Understanding HLA-F peptide selection and presentation is essential to a comprehensive understanding of this dynamic immune response and the molecules function. In this study, we were able to recover stable pHLA-F*01:01 complexes and analyze the characteristics of peptides naturally presented by HLA-F. These HLA-F-restricted peptides exhibit a non-canonical length without a defined N-terminal anchor. The peptide characteristics lead to a unique presentation profile and influence the stability of the protein. Furthermore, we demonstrate that almost all source proteins of HLA-F-restricted peptides are described to interact with HIV proteins. Understanding the balance switch between HLA-Ia and HLA-F expression and peptide selection will support to understand the role of HLA-F in viral pathogenesis. Electronic supplementary material The online version of this article (10.1007/s00251-019-01112-1) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

HLA-F*01:01 presents peptides with N-terminal flexibility and a preferred length of 16 residues

et al. 2019

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“…These findings suggest that the contribution of NK cell KIR polymorphisms to GVL alloreactivity is weak and likely surpassed by other immunologic variables or stronger clinical factors such as HLA matching, disease status, and in vivo T cell depletion. For example, CLL cells have been shown to overexpress HLA-E, the natural ligand for the inhibitory receptor NKG2A expressed on NK cells [21]. NKG2A/HLA-E interaction has been shown to be a mechanism of tumor evasion in CLL patients and may be a mechanism relevant for immune escape from GVL [22].…”

Section: Discussionmentioning

confidence: 99%

Donor Killer Cell Immunoglobulin-Like Receptor Genotype Does Not Improve Graft-versus-Leukemia Responses in Chronic Lymphocytic Leukemia after Unrelated Donor Transplant: A Center for International Blood and Marrow Transplant Research Analysis

Bachanová

Weisdorf

Wang

et al. 2019

Biology of Blood and Marrow Transplantation

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Allogeneic hematopoietic cell transplantation (alloHCT) remains the sole curative therapy for patients with chronic lymphocytic leukemia (CLL), leading to 40% to 45% long-term survival. The impact of donor killer immunoglobulin-like receptor (KIR) genotype on outcomes of unrelated donor (URD) alloHCT for CLL is unknown. We examined 573 adult URD CLL recipient pairs. KIR genotype (presence/absence) was determined for each donor, and comprehensive modeling of interactions with recipient HLA class I loci (KIR ligands) was used to evaluate their effect on relapse and survival. Recipients had a median age of 56 years, and most were not in remission (65%). Both 8/8 HLA-matched (81%) or 7/8 HLA matched grafts (19%) were studied. Factors associated with improved overall survival (OS) were reduced-intensity conditioning (hazard ratio [HR] of death, .76) and good performance status (HR, .46), whereas alloHCT in nonremission (HR, 1.96) and mismatched donors (HR, 2.01) increased mortality. No models demonstrated a relationship between donor KIR genotype and transplant outcomes. Cox regression models comparing donors with A/A versus B/x KIR haplotypes and those with KIR gene content scores of 0 versus 1 versus 2 yielded similar rates of nonrelapse mortality, relapse, acute graft-versus-host disease (GVHD), and chronic GVHD and the same progression-free survival and OS. Relapse risk was not different for grafts from donors with KIR3DL1 transplanted into HLA C1/ 1 versus C2 recipients. This large analysis failed to demonstrate an association between URD KIR genotype and transplant outcome for patients with CLL, and thus KIR genotyping should not be used as a donor selection criterion in this setting.

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“…In particular, soluble HLA-E and HLA-G are in the focus, because their expression is highly associated with the disease progression in tumor cells. In case of HLA-E, soluble molecules were significantly increased in neuroblastoma [51], melanoma [52] and chronic lymphocytic leukemia [53]. However, the overexpression of HLA-E is associated with the inhibition of tumor infiltrating NK cells and CD94 + /NKG2A + CTLs and contributes as one factor for the immune evasion strategies of tumor cells.…”

Section: The Multiple Roles Of Hla-e In Immune System (A) Hla-e Presmentioning

confidence: 99%

Dynamic Interaction between Immune Escape Mechanism and HLA-Ib Regulation

Hò¹,

Heinen²,

Stieglitz³

et al. 2019

Immunogenetics

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HLA molecules scan the intracellular proteome and present self-or non-selfpeptides to immune effector cells. HLA-Ia (HLA-A, HLA-B and HLA-C) are the most polymorphic genes, resulting in various numbers of allelic variants expressed on the surface of almost all nucleated cells. In contrast to HLA-Ia molecules that activate the immune system during pathogenic invasion, the marginal polymorphic HLA-Ib molecules (HLA-E, HLA-F and HLA-G) are upregulated during pathogenic episodes and mediate immune tolerance. A fine tuning between downregulation of HLA-Ia and upregulation of HLA-Ib can be observed through immunological episodes that require to remain unrecognized by immune effector cells. While HLA-Ia molecules collaborate by presenting a wide range of peptides, every HLA-Ib molecule is highly specialized in its protective immune function and seems to be restricted in the presentation of peptides. Additionally, Ia molecules are expressed ubiquitously while the expression of HLA-Ib molecules is strictly restricted to certain tissues and occurs instantly on demand of the cells/tissue that attempt to be hidden from the immune system. The more knowledge becomes available for the function of HLA-Ib molecules; the question emerges if the molecular typing of HLA-Ib molecules would be reasonable to take a decision post treatment for personalized cellular therapies.

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HLA‐E allelic genotype correlates with HLA‐E plasma levels and predicts early progression in chronic lymphocytic leukemia

Abstract: HLA-E alleles and sHLA-E levels may represent novel biomarkers for early disease progression in patients with CLL. Cancer 2017;123:814-23. © 2016 American Cancer Society.

Cited by 37 publications

References 57 publications

HLA-F*01:01 presents peptides with N-terminal flexibility and a preferred length of 16 residues

HLA-F*01:01 presents peptides with N-terminal flexibility and a preferred length of 16 residues

Donor Killer Cell Immunoglobulin-Like Receptor Genotype Does Not Improve Graft-versus-Leukemia Responses in Chronic Lymphocytic Leukemia after Unrelated Donor Transplant: A Center for International Blood and Marrow Transplant Research Analysis

Dynamic Interaction between Immune Escape Mechanism and HLA-Ib Regulation

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