scholarly journals High resolution profiling of MHC-II peptide presentation capacity, by Mammalian Epitope Display, reveals SARS-CoV-2 targets for CD4 T cells and mechanisms of immune-escape

2021 ◽  
Author(s):  
Franz Josef Obermair ◽  
Florian Renoux ◽  
Sebastian Heer ◽  
Chloe Lee ◽  
Nastassja Cereghetti ◽  
...  
Keyword(s):  
T Cell ◽  
High Resolution ◽  
Immune Evasion ◽  
Immune Escape ◽  
Class Ii ◽  
Hla Class Ii ◽  
Effective Response ◽  
Mhc Ii ◽  
Cell Immunity ◽  
Peptide Presentation

Understanding the mechanisms of immune evasion is critical for formulating an effective response to global threats like SARS-CoV2. We have fully decoded the immune synapses for multiple TCRs from acute patients, including cognate peptides and the presenting HLA alleles. Furthermore, using a newly developed mammalian epitope display platform (MEDi), we determined that several mutations present in viral isolates currently expanding across the globe, resulted in reduced presentation by multiple HLA class II alleles, while some increased presentation, suggesting immune evasion based on shifting MHC-II peptide presentation landscapes. In support, we found that one of the mutations present in B1.1.7 viral strain could cause escape from CD4 T cell recognition in this way. Given the importance of understanding such mechanisms more broadly, we used MEDi to generate a comprehensive analysis of the presentability of all SARS-CoV-2 peptides in the context of multiple common HLA class II molecules. Unlike other strategies, our approach is sensitive and scalable, providing an unbiased and affordable high-resolution map of peptide presentation capacity for any MHC-II allele. Such information is essential to provide insight into T cell immunity across distinct HLA haplotypes across geographic and ethnic populations. This knowledge is critical for the development of effective T cell therapeutics not just against COVID-19, but any disease.

scholarly journals Rapid Generation of Sustainable HER2-specific T-cell Immunity in Patients with HER2 Breast Cancer using a Degenerate HLA Class II Epitope Vaccine

2019 ◽  
Vol 26 (5) ◽  
pp. 1045-1053 ◽  
Author(s):  
Keith L. Knutson ◽  
Matthew S. Block ◽  
Nadine Norton ◽  
Courtney L. Erskine ◽  
Timothy J. Hobday ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Class Ii ◽  
Hla Class Ii ◽  
T Cell Immunity ◽  
Epitope Vaccine ◽  
Her2 Breast Cancer ◽  
Cell Immunity ◽  
Rapid Generation

scholarly journals Epstein-Barr Virus gp42 Is Posttranslationally Modified To Produce Soluble gp42 That Mediates HLA Class II Immune Evasion

2005 ◽  
Vol 79 (2) ◽  
pp. 841-852 ◽  
Author(s):  
Maaike E. Ressing ◽  
Daphne van Leeuwen ◽  
Frank A. W. Verreck ◽  
Sinéad Keating ◽  
Raquel Gomez ◽  
...  
Keyword(s):  
T Cell ◽  
Epstein Barr Virus ◽  
Human Leukocyte ◽  
Class Ii ◽  
Hla Class Ii ◽  
Lytic Cycle ◽  
Soluble Form ◽  
Barr Virus ◽  
Cell Immunity ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) resides as a persistent infection in human leukocyte antigen (HLA) class II+ B lymphocytes and is associated with a number of malignancies. The EBV lytic-phase protein gp42 serves at least two functions: gp42 acts as the coreceptor for viral entry into B cells and hampers T-cell recognition via HLA class II molecules through steric hindrance of T-cell receptor-class II-peptide interactions. Here, we show that gp42 associates with class II molecules at their various stages of maturation, including immature αβIi heterotrimers and mature αβ-peptide complexes. When analyzing the biosynthesis and maturation of gp42 in cells stably expressing the viral protein, we found that gp42 occurs in two forms: a full-length type II membrane protein and a truncated soluble form. Soluble gp42 is generated by proteolytic cleavage in the endoplasmic reticulum and is secreted. Soluble gp42 is sufficient to inhibit HLA class II-restricted antigen presentation to T cells. In an almost pure population of Burkitt's lymphoma cells in the EBV lytic cycle, both transmembrane and soluble forms of gp42 are detected. These results imply that soluble gp42 is generated during EBV lytic infection and could contribute to undetected virus production by mediating evasion from T-cell immunity.

P018. A long peptide from MELOE-1 contains multiple HLA class II T cell epitopes in addition to the HLA-A*0201 epitope

2011 ◽  
Vol 21 ◽  
pp. e26-e27
Author(s):  
A. Rogel ◽  
V. Vignard ◽  
M. Bobinet ◽  
N. Labarrière ◽  
F. Lang
Keyword(s):  
T Cell ◽  
Class Ii ◽  
Hla Class Ii ◽  
T Cell Epitopes

Transfected murine cells expressing HLA class II can be used to generate alloreactive human T cell clones

1994 ◽  
Vol 169 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Anthony N. Warrens ◽  
Tricia Heaton ◽  
Sid Sidhu ◽  
Giovanna Lombardi ◽  
Robert I. Lechler
Keyword(s):  
T Cell ◽  
Class Ii ◽  
Hla Class Ii ◽  
T Cell Clones ◽  
Human T Cell ◽  
Cell Clones

scholarly journals High-resolution mapping identifies HLA class II associations with multifocal motor neuropathy

2021 ◽  
Vol 101 ◽  
pp. 79-84
Author(s):  
Jeroen W. Bos ◽  
Henny G. Otten ◽  
Ingrid J.T. Herraets ◽  
H. Stephan Goedee ◽  
E.A. Cats ◽  
...  
Keyword(s):  
High Resolution ◽  
Multifocal Motor Neuropathy ◽  
Class Ii ◽  
Hla Class Ii ◽  
Motor Neuropathy ◽  
High Resolution Mapping ◽  
Resolution Mapping

scholarly journals Human T-Cell Leukemia Virus Type II Directly Acts on CD34+ Hematopoietic Precursors by Increasing Their Survival Potential. Envelope-Associated HLA Class II Molecules Reverse This Effect

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2296-2304
Author(s):  
Claudio Casoli ◽  
Maria Carla Re ◽  
Paola Monari ◽  
Giuliano Furlini ◽  
Giovanna Tosi ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Class Ii ◽  
Hla Class Ii ◽  
Type Ii ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

The role of human T-cell leukemia virus type II (HTLV-II) in human lymphoproliferative and hematopoietic abnormalities in which the retrovirus can be isolated is still elusive. Here we show that the C344 T-cell–derived lymphotropic HTLV-II type IIa Mo strain acts directly on CD34+ hematopoietic precursors by rescuing them from apoptosis induced by interleukin-3 (IL-3) deprivation. This effect is viral strain-specific, as it is not observed with the B-lymphotropic HTLV-II type IIb Gu strain, it does not require infection of the hematopoietic precursors, and, interestingly, it is strongly dependent on the infected cellular host from which the virus was derived. Indeed, growth adaptation of the Mo strain to the permissive B-cell line, BJAB, renders the virus no longer capable of mediating the antiapoptotic effect. However, pretreatment of the BJAB-adapted Mo strain with antibodies specific for HLA class II, but not class I, histocompatibility antigens restores the antiapoptotic potential of the virus. These results constitute the first evidence that HTLV-II retrovirus can directly influence the homeostasis of human progenitors, without infecting them, and that this crucial activity is strongly inhibited by the presence of host-derived envelope-associated HLA class II antigens.

Automated DNA Sequencing — a fast and accurate method for high resolution HLA class II typing

1996 ◽  
Vol 47 (1-2) ◽  
pp. 114
Author(s):  
Martina Bielefeld ◽  
Ella van den Berg-Loonen ◽  
Paul Savelkou ◽  
Lennart Björkesten
Keyword(s):  
High Resolution ◽  
Dna Sequencing ◽  
Accurate Method ◽  
Class Ii ◽  
Hla Class Ii ◽  
Automated Dna Sequencing

Recognition of naturally processed and ovarian cancer reactive CD8+ T cell epitopes within a promiscuous HLA class II T-helper region of NY-ESO-1

2008 ◽  
Vol 57 (8) ◽  
pp. 1185-1195 ◽  
Author(s):  
Junko Matsuzaki ◽  
Feng Qian ◽  
Immanuel Luescher ◽  
Shashikant Lele ◽  
Gerd Ritter ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cell ◽  
Cd8 T Cell ◽  
Class Ii ◽  
Hla Class Ii ◽  
T Cell Epitopes ◽  
T Helper

scholarly journals Functional interaction between human histocompatibility leukocyte antigen (HLA) class II and mouse CD4 molecule in antigen recognition by T cells in HLA-DR and DQ transgenic mice.

1994 ◽  
Vol 180 (1) ◽  
pp. 165-171 ◽  
Author(s):  
K Yamamoto ◽  
Y Fukui ◽  
Y Esaki ◽  
T Inamitsu ◽  
T Sudo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Responses ◽  
Class Ii ◽  
Hla Class Ii ◽  
Functional Interaction ◽  
Leukocyte Antigen ◽  
Cell Responses ◽  
Hla Class Ii Molecules

Studies in vitro have suggested that a species barrier exists in functional interaction between human histocompatibility leukocyte antigen (HLA) class II and mouse CD4 molecules. However, whether mouse CD4+ T cells restricted by HLA class II molecules are generated in HLA class II transgenic mice and respond to peptide antigens across this barrier has remained unclear. In an analysis of T cell responses to synthetic peptides in mice transgenic for HLA-DR51 and -DQ6, we found that DR51 and DQ6 transgenic mice acquired significant T cell response to influenza hemagglutinin-derived peptide 307-319 (HA 307) and Streptococcus pyogenes M12 protein-derived peptide 347-397 (M6C2), respectively. Inhibition studies with several monoclonal antibodies showed that transgenic HLA class II molecules presented these peptides to mouse CD4+ T cells. Furthermore, T cell lines specific for HA 307 or M6C2 obtained from the transgenic mice could respond to the peptide in the context of relevant HLA class II molecules expressed on mouse L cell transfectants that lack the expression of mouse MHC class II. These findings indicate that interaction between HLA class II and mouse CD4 molecules is sufficient for provoking peptide-specific HLA class II-restricted T cell responses in HLA class II transgenic mice.

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