Many viral antigens have been identified in patients with COVID-19 patients, but which of these result in meaningful immune responses is unclear. Here the authors identify a range of SARS-CoV-2 CD8... Show moreMany viral antigens have been identified in patients with COVID-19 patients, but which of these result in meaningful immune responses is unclear. Here the authors identify a range of SARS-CoV-2 CD8(+) T cell responses across patients including a response targeting an epitope of ORF1ab with immunodominant properties.The COVID-19 pandemic caused by SARS-CoV-2 is a continuous challenge worldwide, and there is an urgent need to map the landscape of immunogenic and immunodominant epitopes recognized by CD8(+) T cells. Here, we analyze samples from 31 patients with COVID-19 for CD8(+) T cell recognition of 500 peptide-HLA class I complexes, restricted by 10 common HLA alleles. We identify 18 CD8(+) T cell recognized SARS-CoV-2 epitopes, including an epitope with immunodominant features derived from ORF1ab and restricted by HLA-A*01:01. In-depth characterization of SARS-CoV-2-specific CD8(+) T cell responses of patients with acute critical and severe disease reveals high expression of NKG2A, lack of cytokine production and a gene expression profile inhibiting T cell re-activation and migration while sustaining survival. SARS-CoV-2-specific CD8(+) T cell responses are detectable up to 5 months after recovery from critical and severe disease, and these responses convert from dysfunctional effector to functional memory CD8(+) T cells during convalescence. Show less
Tumors with an impaired transporter associated with antigen processing (TAP) present several endoplasmic reticulum-derived self-antigens on HLA class I (HLA-I) which are absent on healthy cells.... Show moreTumors with an impaired transporter associated with antigen processing (TAP) present several endoplasmic reticulum-derived self-antigens on HLA class I (HLA-I) which are absent on healthy cells. Selection of such TAP-independent antigens for T cell-based immunotherapy should include analysis of their expression on healthy cells to prevent therapy-induced adverse toxicities. However, it is unknown how the absence of clinically relevant antigens on healthy cells needs to be validated. Here, we monitored TAP-independent antigen presentation on various healthy cells after establishing a T cell tool recognizing a TAP-independent signal sequence receptor 1-derived antigen. We found that most but not all healthy cells present this antigen under normal and inflammatory conditions, indicating that TAP-independent antigen presentation is a variable phenomenon. Our data emphasize the necessity of extensive testing of a wide variety of healthy cell types to define clinically relevant TAP-independent antigens that can be safely targeted by immunotherapy. Show less
A single model system for integrative studies on multiple facets of antigen presentation is lacking. PAKC is a novel panel of ten cell lines knocked out for individual components of the HLA class I... Show moreA single model system for integrative studies on multiple facets of antigen presentation is lacking. PAKC is a novel panel of ten cell lines knocked out for individual components of the HLA class I antigen presentation pathway. PAKC will accelerate HLA-I research in the fields of oncology, infectiology, and autoimmunity. Show less
Land-Zandstra, A.M.; Hoefakker, K.; Damsma, W. 2020
In natural history museums, a large part of the educational mission is to facilitate family learning with and about objects. Questions on object labels can play a role in this learning process. In... Show moreIn natural history museums, a large part of the educational mission is to facilitate family learning with and about objects. Questions on object labels can play a role in this learning process. In the current study, we investigated the effect that different types of questions on object labels can have on the reasoning conversations among family members. We audio-recorded family conversations at an exhibit that included a fossilized dinosaur egg and a text label containing a question. Sixty-six families participated in three conditions differing in the level of complexity of the question on the label. We found that a question of moderate complexity facilitated the longest conversations, with the largest number of complex inferences, compared to the simpler and the more complex question. When reasoning, families most often used evidence from prior knowledge and other parts of the exhibition, but did not often relate to personal experiences. During the longer and more complex conversations, parents took up a larger role in the conversation, facilitating their family's reasoning process. We suggest that open-ended, moderately complex questions on labels can facilitate family reasoning conversations. Providing enough context within the surrounding exhibits and connecting to prior knowledge may help the reasoning process. Show less
