T cell recognition of a tumor-associated glycoprotein and its synthetic carbohydrate epitopes: stimulation of anticancer T cell immunity in vivo

1987 ◽  
Vol 25 (3) ◽  
Author(s):  
CarinaM. Henningsson ◽  
Subnaicker Selvaraj ◽  
GrantD. MacLean ◽  
MavanurR. Suresh ◽  
AntoineA. Noujaim ◽  
...  
2021 ◽  
Vol 6 (58) ◽  
pp. eabf7550
Author(s):  
Sunil Kumar Saini ◽  
Ditte Stampe Hersby ◽  
Tripti Tamhane ◽  
Helle Rus Povlsen ◽  
Susana Patricia Amaya Hernandez ◽  
...  

T cells are important for effective viral clearance, elimination of virus-infected cells and long-term disease protection. To examine the full-spectrum of CD8+ T cell immunity in COVID-19, we experimentally evaluated 3141 major histocompatibility (MHC) class I-binding peptides covering the complete SARS-CoV-2 genome. Using DNA-barcoded peptide-MHC complex (pMHC) multimers combined with a T cell phenotype panel, we report a comprehensive list of 122 immunogenic and a subset of immunodominant SARS-CoV-2 T cell epitopes. Substantial CD8+ T cell recognition was observed in COVID-19 patients, with up to 27% of all CD8+ lymphocytes interacting with SARS-CoV-2-derived epitopes. Most immunogenic regions were derived from open reading frame (ORF) 1 and ORF3, with ORF1 containing most of the immunodominant epitopes. CD8+ T cell recognition of lower affinity was also observed in healthy donors toward SARS-CoV-2-derived epitopes. This pre-existing T cell recognition signature was partially overlapping with the epitope landscape observed in COVID-19 patients and may drive the further expansion of T cell responses to SARS-CoV-2 infection. Importantly the phenotype of the SARS-CoV-2-specific CD8+ T cells, revealed a strong T cell activation in COVID-19 patients, while minimal T cell activation was seen in healthy individuals. We found that patients with severe disease displayed significantly larger SARS-CoV-2-specific T cell populations compared to patients with mild diseases and these T cells displayed a robust activation profile. These results further our understanding of T cell immunity to SARS-CoV-2 infection and hypothesize that strong antigen-specific T cell responses are associated with different disease outcomes.


2021 ◽  
Vol 11 ◽  
Author(s):  
Alex Olvera ◽  
Samandhy Cedeño ◽  
Anuska Llano ◽  
Beatriz Mothe ◽  
Jorge Sanchez ◽  
...  

It is largely unknown how post-translational protein modifications, including glycosylation, impacts recognition of self and non-self T cell epitopes presented by HLA molecules. Data in the literature indicate that O- and N-linked glycosylation can survive epitope processing and influence antigen presentation and T cell recognition. In this perspective, we hypothesize that glycosylation of viral proteins and processed epitopes contribute to the T cell response to HIV. Although there is some evidence for T cell responses to glycosylated epitopes (glyco-epitopes) during viral infections in the literature, this aspect has been largely neglected for HIV. To explore the role of glyco-epitope specific T cell responses in HIV infection we conducted in silico and ex vivo immune studies in individuals with chronic HIV infection. We found that in silico viral protein segments with potentially glycosylable epitopes were less frequently targeted by T cells. Ex vivo synthetically added glycosylation moieties generally masked T cell recognition of HIV derived peptides. Nonetheless, in some cases, addition of simple glycosylation moieties produced neo-epitopes that were recognized by T cells from HIV infected individuals. Herein, we discuss the potential importance of these observations and compare limitations of the employed technology with new methodologies that may have the potential to provide a more accurate assessment of glyco-epitope specific T cell immunity. Overall, this perspective is aimed to support future research on T cells recognizing glycosylated epitopes in order to expand our understanding on how glycosylation of viral proteins could alter host T cell immunity against viral infections.


2011 ◽  
Vol 188 (2) ◽  
pp. 892-901 ◽  
Author(s):  
Xiang Xiao ◽  
Weihua Gong ◽  
Gulcin Demirci ◽  
Wentao Liu ◽  
Silvia Spoerl ◽  
...  

1980 ◽  
Vol 3 (2) ◽  
pp. 213-245 ◽  
Author(s):  
J. Sprent ◽  
R. Korngold ◽  
K. Molnar-Kimber

1988 ◽  
Vol 19 (1) ◽  
pp. 41-47
Author(s):  
K. Mizoguchi ◽  
K. Isobe ◽  
T. Yoshida ◽  
T. Iwamoto ◽  
T. Hasegawa ◽  
...  

2002 ◽  
Vol 196 (10) ◽  
pp. 1277-1290 ◽  
Author(s):  
Ryohei F. Tsuji ◽  
Marian Szczepanik ◽  
Ivana Kawikova ◽  
Vipin Paliwal ◽  
Regis A. Campos ◽  
...  

Contact sensitivity (CS) is a classic example of in vivo T cell immunity in which skin sensitization with reactive hapten leads to immunized T cells, which are then recruited locally to mediate antigen-specific inflammation after subsequent skin challenge. We have previously shown that T cell recruitment in CS is triggered by local activation of complement, which generates C5a that triggers C5a receptors most likely on mast cells. Here, we show that B-1 cell–derived antihapten IgM antibodies generated within 1 day (d) of immunization combine with local challenge antigen to activate complement to recruit the T cells. These findings overturn three widely accepted immune response paradigms by showing that (a) specific IgM antibodies are required to initiate CS, which is a classical model of T cell immunity thought exclusively due to T cells, (b) CS priming induces production of specific IgM antibodies within 1 d, although primary antibody responses typically begin by day 4, and (c) B-1 cells produce the 1-d IgM response to CS priming, although these cells generally are thought to be nonresponsive to antigenic stimulation. Coupled with previous evidence, our findings indicate that the elicitation of CS is initiated by rapidly formed IgM antibodies. The IgM and challenge antigen likely form local complexes that activate complement, generating C5a, leading to local vascular activation to recruit the antigen-primed effector T cells that mediate the CS response.


2008 ◽  
Vol 181 (11) ◽  
pp. 7721-7727 ◽  
Author(s):  
Amy K. Wesa ◽  
Christopher J. Herrem ◽  
Maja Mandic ◽  
Jennifer L. Taylor ◽  
Cecilia Vasquez ◽  
...  

1989 ◽  
Vol 169 (5) ◽  
pp. 1655-1668 ◽  
Author(s):  
M Pierres ◽  
S Marchetto ◽  
P Naquet ◽  
D Landais ◽  
J Peccoud ◽  
...  

An individual's T lymphocytes are highly reactive to allogeneic MHC molecules. As a step in deciphering the mechanism of allorecognition by T lymphocytes, we have attempted to identify the TCR's target on MHC class II molecules, in particular the polymorphic residues that determine the specificity of recognition. We have generated a panel of Ak-reactive, Ab-nonreactive T cell hybridomas, and sets of L cell transfectants displaying A alpha A beta molecules with wild-type, chimeric or single site-mutated A alpha chains, with reciprocal interchanges between Ak and Ab. We then measured the stimulation of the T hybridomas in response to the transfectants. The results indicate that the hybridomas recognize diverse and complex determinants, with contributions from both A alpha and A beta chains, and from several regions or amino acids of the A alpha chain. The data are most consistent with a model in which alloreactivity results from the presentation of peptides to the T cell by an allogeneic MHC molecule, peptides that cannot be presented by the responder's own MHC complexes. The specificity of allorecognition seems to be imparted mainly by peptide/MHC molecule rather than TCR/MHC molecule contacts.


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