Upregulation of HLA class I and antiviral immune responses in graves’ disease

2020 ◽  
Author(s):  
Therese Weider ◽  
Sarah Richardson ◽  
Noel G. Morgan ◽  
Trond H. Paulsen ◽  
Knut Dahl-Jørgensen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Hla Class I ◽  
Class I ◽  
Graves Disease

scholarly journals HLA tapasin independence: broader peptide repertoire and HIV control

2020 ◽  
Vol 117 (45) ◽  
pp. 28232-28238 ◽  
Author(s):  
Arman A. Bashirova ◽  
Mathias Viard ◽  
Vivek Naranbhai ◽  
Alba Grifoni ◽  
Wilfredo Garcia-Beltran ◽  
...  
Keyword(s):  
Immune Responses ◽  
Ex Vivo ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Cytotoxic T Cell ◽  
Leukocyte Antigen ◽  
Viral Loads ◽  
Peptide Loading ◽  
Cytotoxic T Cell Responses

Human leukocyte antigen (HLA) class I allotypes vary in their ability to present peptides in the absence of tapasin, an essential component of the peptide loading complex. We quantified tapasin dependence of all allotypes that are common in European and African Americans (n= 97), which revealed a broad continuum of values. Ex vivo examination of cytotoxic T cell responses to the entire HIV-1 proteome from infected subjects indicates that tapasin-dependent allotypes present a more limited set of distinct peptides than do tapasin-independent allotypes, data supported by computational predictions. This suggests that variation in tapasin dependence may impact the strength of the immune responses by altering peptide repertoire size. In support of this model, we observed that individuals carryingHLA class Igenotypes characterized by greater tapasin independence progress more slowly to AIDS and maintain lower viral loads, presumably due to increased breadth of peptide presentation. Thus, tapasin dependence level, likeHLAzygosity, may serve as a means to restrict or expand breadth of the HLA-I peptide repertoire across humans, ultimately influencing immune responses to pathogens and vaccines.

scholarly journals Immunoproteomic Lessons for Human Respiratory Syncytial Virus Vaccine Design

2019 ◽  
Vol 8 (4) ◽  
pp. 486
Author(s):  
López ◽  
Barriga ◽  
Lorente ◽  
Mir
Keyword(s):  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Antigen Processing ◽  
Hla Class I ◽  
Human Respiratory Syncytial Virus ◽  
Class I ◽  
Antigenic Peptides ◽  
Cellular Immune Responses ◽  
Syncytial Virus ◽  
Cellular Immune

Accurate antiviral humoral and cellular immune responses require prior recognition of antigenic peptides presented by human leukocyte antigen (HLA) class I and II molecules on the surface of antigen-presenting cells. Both the helper and the cytotoxic immune responses are critical for the control and the clearance of human respiratory syncytial virus (HRSV) infection, which is a significant cause of morbidity and mortality in infected pediatric, immunocompromised and elderly populations. In this article we review the immunoproteomics studies which have defined the general antigen processing and presentation rules that determine both the immunoprevalence and the immunodominance of the cellular immune response to HRSV. Mass spectrometry and functional analyses have shown that the HLA class I and II cellular immune responses against HRSV are mainly focused on three viral proteins: fusion, matrix, and nucleoprotein. Thus, these studies have important implications for vaccine development against this virus, since a vaccine construct including these three relevant HRSV proteins could efficiently stimulate the major components of the adaptive immune system: humoral, helper, and cytotoxic effector immune responses.

HLA class I and II antigens in South African Blacks with Graves' disease

1990 ◽  
Vol 54 (1) ◽  
pp. 98-102 ◽  
Author(s):  
Mahomed A.K. Omar ◽  
Michael G. Hammond ◽  
Rajesh K. Desai ◽  
Ayesha A. Motala ◽  
Nazimuddin Aboo ◽  
...  
Keyword(s):  
South African ◽  
Hla Class I ◽  
Class I ◽  
Graves Disease

Cross-clade immune responses to Gag p24 in patients infected with different HIV-1 subtypes and correlation with HLA class I and II alleles

Vaccine ◽  
2008 ◽  
Vol 26 (40) ◽  
pp. 5182-5187 ◽  
Author(s):  
L. Gudmundsdotter ◽  
D. Bernasconi ◽  
B. Hejdeman ◽  
E. Sandstrom ◽  
A. Alaeus ◽  
...  
Keyword(s):  
Immune Responses ◽  
Hla Class I ◽  
Class I ◽  
Hiv 1

scholarly journals The SPPL3-defined glycosphingolipid repertoire orchestrates HLA class I-mediated immune responses

Immunity ◽  
2021 ◽  
Vol 54 (2) ◽  
pp. 387 ◽  
Author(s):  
Marlieke L.M. Jongsma ◽  
Antonius A. de Waard ◽  
Matthijs Raaben ◽  
Tao Zhang ◽  
Birol Cabukusta ◽  
...  
Keyword(s):  
Immune Responses ◽  
Hla Class I ◽  
Class I

scholarly journals Genetic Modification of Limbal Stem Cells to Decrease Allogeneic Immune Responses

2021 ◽  
Vol 12 ◽  
Author(s):  
Emilio Valdivia ◽  
Marina Bertolin ◽  
Claudia Breda ◽  
Marco Carvalho Oliveira ◽  
Anna Katharina Salz ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Genetic Modification ◽  
Hla Class I ◽  
Class Ii ◽  
Class I ◽  
Limbal Stem Cells ◽  
Term Survival ◽  
Efficient Treatment

Limbal stem cell (LSC) transplantation is the only efficient treatment for patients affected by LSC deficiency (LSCD). Allogeneic LSC transplantation is one of the most successful alternative for patients with bilateral LSCD. Nevertheless, the high variability of the human leukocyte antigens (HLA) remains a relevant obstacle to long-term allogeneic graft survival. This study characterized the immunologic properties of LSCs and proposed a genetic engineering strategy to reduce the immunogenicity of LSCs and of their derivatives. Hence, LSC HLA expression was silenced using lentiviral vectors encoding for short hairpin (sh) RNAs targeting β2-microglobulin (β2M) or class II major histocompatibility complex transactivator (CIITA) to silence HLA class I and II respectively. Beside the constitutive expression of HLA class I, LSCs showed the capability to upregulate HLA class II expression under inflammatory conditions. Furthermore, LSCs demonstrated the capability to induce T-cell mediated immune responses. LSCs phenotypical and functional characteristics are not disturbed after genetic modification. However, HLA silenced LSC showed to prevent T cell activation, proliferation and cytotoxicity in comparison to fully HLA-expressing LSCs. Additionally; HLA-silenced LSCs were protected against antibody-mediated cellular-dependent cytotoxicity. Our data is a proof-of-concept of the feasibility to generate low immunogenic human LSCs without affecting their typical features. The use of low immunogenic LSCs may support for long-term survival of LSCs and their derivatives after allogeneic transplantation.

scholarly journals The SPPL3-defined glycosphingolipid repertoire regulates immune responses by improving HLA class I access

2020 ◽  
Author(s):  
Marlieke L.M. Jongsma ◽  
Matthijs Raaben ◽  
Antonius A. de Waard ◽  
Tao Zhang ◽  
Birol Cabukusta ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Cell Activation ◽  
Patient Survival ◽  
Hla Class I ◽  
Class I ◽  
Potential Therapeutic Target ◽  
Genome Wide ◽  
Approved Drugs

SummaryHLA class I (HLA-I) drives immune responses by presenting antigen-derived peptides to cognate CD8+ T cells. This process is often hijacked by tumors and pathogens for immune evasion. Since therapeutic options for restoring HLA-I antigen presentation are limited, we aimed to identify new HLA-I pathway targets. By iterative genome-wide screens we uncovered that the cell surface glycosphingolipid (GSL) repertoire determines effective HLA-I antigen presentation. We show that absence of the protease SPPL3 augments B3GNT5 enzyme activity, resulting in upregulated levels of surface (neo)lacto-series GSLs. These GSLs sterically impede molecular interactions with HLA-I and diminish CD8+ T cell activation. In accordance, a disturbed SPPL3-B3GNT5 pathway in glioma associates with decreased patient survival. Importantly, we show that this immunomodulatory effect can be reversed through GSL synthesis inhibition using clinically approved drugs. Overall, our study identifies a GSL signature that functionally inhibits antigen presentation and represents a potential therapeutic target in cancer, infection and autoimmunity.

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