ResearchPad - reflections https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Navigating the emotional turmoil of the COVID-19 pandemic as a new leader]]> https://www.researchpad.co/article/elastic_article_12443 In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

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<![CDATA[The ABC of Major Histocompatibility Complexes and T Cell Receptors in Health and Disease]]> https://www.researchpad.co/article/Nffb610d1-9f53-4e4d-8276-844e9f10f6c7 A seminal discovery of major histocompatibility complex (MHC) restriction in T cell recognition by Peter Doherty and Rolf Zinkernagel has led to 45 years of exciting research on the mechanisms governing peptide MHC (pMHC) recognition by T cell receptors (TCRs) and their importance in health and disease. T cells provide a significant level of protection against viral, bacterial, and parasitic infections, as well as tumors, hence, the generation of protective T cell responses is a primary goal for cell-mediated vaccines and immunotherapies. Understanding the mechanisms underlying generation of optimal high-avidity effector T cell responses, memory development, maintenance, and recall is of major importance for the rational design of preventative and therapeutic vaccines/immunotherapies. In this review, we summarize the lessons learned over the last four decades and outline our current understanding of the basis and consequences of pMHC/TCR interactions on T cell development and function, and TCR diversity and composition, driving better clinical outcomes and prevention of viral escape. We also discuss the current models of T cell memory formation and determinants of immunodominant T cell responses in animal models and humans. As TCR composition and diversity can affect both the protective capacity of T cells and protection against viral escape, defining the spectrum of TCR selection has implications for improving the functional efficacy of effector T cell responsiveness and memory formation.

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<![CDATA[The Education of Future Immunologists: Lessons from the Doherty Lab]]> https://www.researchpad.co/article/N6e475139-5f49-4a32-bb9e-d00d99e01cd0 <![CDATA[Peter C. Doherty: A Legacy of Mentoring]]> https://www.researchpad.co/article/N0e5522b0-d46a-4fdc-9f79-60a1f37ce06f <![CDATA[Reflections from Peter's First Graduate Student]]> https://www.researchpad.co/article/Ned57c4d6-ef5f-4a75-bf84-db44742b8575 <![CDATA[A Disquisition on MHC Restriction and T Cell Recognition in Five Acts]]> https://www.researchpad.co/article/N94b7c308-084b-45bb-a8bc-9907a639be2b The seminal discovery in the early 1970s, credited to Peter Doherty and Rolf Zinkernagel, of major histocompatibility complex (MHC) restriction exhibited by cytotoxic T cells represented a major conceptual advance in understanding antigen recognition by conventional T cells. This advance also led to other major new insights into the ontogeny and immunobiology of T cells and catalyzed a renaissance in viral immunology. In this commentary in honor of Peter Doherty, I offer five brief reflections on different aspects of the phenomenon of MHC restriction and the process by which it was discovered and explained. In the first of these sections, I offer a reinterpretation of MHC restriction that reframes the constraints on self-MHC recognition in terms of the probabilities of recognizing a given nominal antigen peptide in the context of an MHC molecule that is nonself on the basis of differing in amino acid sequence from the self-restriction element at one or more positions. Subsequent sections address: (i) the ways in which general ideas, developed subsequent to the discovery of MHC restriction, about the intricacies of antigen recognition by antibodies apply to T cell receptors binding to MHC/peptide complexes; (ii) how to reconcile the existence of MHC restriction with the impressive magnitude of T cell responses to nonself MHC antigens; (iii) the possible relevance to MHC restriction and immune system function of ideas from mathematical logic that relate to the consequences of self-reference; and (iv) the implications for the philosophy of science of MHC restriction and the processes of its discovery and acceptance within the immunology research community.

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<![CDATA[Elucidating Specificity Opens a Window to the Complexity of Both the Innate and Adaptive Immune Systems]]> https://www.researchpad.co/article/Nfcd24800-f125-4f5c-9e69-a6588b3cb9d0 Science is a tedious and painstaking business. Many discoveries are considered incremental, individually not necessarily earth shattering, but collectively providing the critical broad framework on which pivotal insights can emerge. Transformational discoveries spring from this knowledge legacy of others and spur a fervent discovery process, often driven by technological developments. The seminal discovery of major histocompatibility class restriction I (MHCI) and its role in antiviral infections by Doherty and Zinkernagel in 1974 was one such discovery—the key that unlocked the treasure chest to the rich tapestry of the diversity of the immune system. An army of researchers have teased apart the different elements of the immune response, which now brings us to a deeper understanding of immune memory and protective immunity. In this process, it has uncovered a multitude of cell types that bridge the innate and adaptive arms of the immune system—blurring the line between these two branches—and ultimately fortifying the development of long-term immune protection.

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<![CDATA[Commentary in Honor of Peter C. Doherty]]> https://www.researchpad.co/article/N0d25dc90-7f07-41e4-b4f2-e07a08033dfe <![CDATA[Serendipity: Reflections on Being Mentored by Dr. Peter Doherty]]> https://www.researchpad.co/article/Ncaaa4b4c-72ad-48c4-8ddd-51d7399af0be This is a semiautobiographical and scientific account of my time in the Doherty Laboratory from 1994 to 1999. It includes personal vignettes as well as discussion of how our work has impacted the fields of influenza, respiratory infections and immunity. I also point out the long-term impacts on my career.

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<![CDATA[Peter Doherty: Role Model and Lifelong Friend]]> https://www.researchpad.co/article/N9bf7b747-a219-4472-8eb6-6fa7f301ab8a <![CDATA[MHC Restriction: Where Are We Now?]]> https://www.researchpad.co/article/Na895b435-62ef-43b1-8111-7daf2f2f158c <![CDATA[No evidence for distinct types in the evolution of SARS-CoV-2]]> https://www.researchpad.co/article/N5f6acc05-2708-40ac-a24b-420e272a5588 A recent study by Tang et al. claimed that two major types of severe acute respiratory syndrome-coronavirus-2 (CoV-2) had evolved in the ongoing CoV disease-2019 pandemic and that one of these types was more ‘aggressive’ than the other. Given the repercussions of these claims and the intense media coverage of these types of articles, we have examined in detail the data presented by Tang et al., and show that the major conclusions of that paper cannot be substantiated. Using examples from other viral outbreaks, we discuss the difficulty in demonstrating the existence or nature of a functional effect of a viral mutation, and we advise against overinterpretation of genomic data during the pandemic.

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<![CDATA[Selecting a SARS-CoV-2/COVID molecular testing method for your laboratory]]> https://www.researchpad.co/article/Nbe27e85a-11eb-4f10-821e-9d02fa75f3a4 In early March 2020 it became apparent that clinical laboratories would need to quickly develop strategies for SARS-CoV-2/COVID-19 testing. For most, the initial approach was to send out testing to a reference laboratory. As the pandemic has progressed, the food and drug administration (FDA) has allowed for several manufacturers to make testing reagents commercially available. Concurrently, the demand for rapid accessibility of results persists, leading many laboratories to evaluate options for “in house” testing. This reflection highlights some of the considerations when selecting the best method for your laboratory, with specific examples highlighted from a medium volume laboratory’s experience.

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<![CDATA[Being Arjuna was Enriching, Being Eklavya is Enlightening!]]> https://www.researchpad.co/article/N69ab0410-1355-4a3f-ab4e-72cc0d1abd69 ]]> <![CDATA[Commentary: Nobody loves a critic: Edmund A Parkes and John Snow’s cholera]]> https://www.researchpad.co/article/Necff5e0b-ef26-4fef-bf75-e28e6a72bc29 ]]> <![CDATA[ASO Author Reflections: Internal Mammary Sentinel Lymph Node Biopsy—Time for the Back of Internal Mammary Staging?]]> https://www.researchpad.co/article/N03981a06-0087-43d0-9a17-6399fb4f3783 ]]> <![CDATA[ASO Author Reflections: Consideration of a Modified Classification System for Gastric Cancer Based on Lauren Subtypes]]> https://www.researchpad.co/article/5c59e20dd5eed0c4841124f3 ]]> <![CDATA[ASO Author Reflections: Hematological Biomarkers of Survival in Cutaneous Melanoma]]> https://www.researchpad.co/article/5c59e214d5eed0c484112529 ]]> <![CDATA[ASO Author Reflections: Toward Improved Selection of Patients for Cytoreduction and HIPEC: Identification of Prognostic Factors for Patients with Colorectal Peritoneal Metastases]]> https://www.researchpad.co/article/5c59e217d5eed0c484112541 ]]> <![CDATA[ASO Author Reflections: Survival Trends in Gastric Adenocarcinoma]]> https://www.researchpad.co/article/5c59e20ed5eed0c4841124ff ]]>