Research group - Annika Karlsson
Our research goal is to define virus-specific T cell immunity in pregnant women, children, adolescents, adults, elderly, and in human cancer with implications for immunopathogenesis, development and regulation of the immune system, and health. We are the link between immune response and health with an empahsize on HIV and SARS-CoV-2 infection.
Understanding cellular and molecular dynamics of viral-specific T cell responses
By adapting bioinformatics my group has established a system to evaluate virus-specific CD4 and CD8 T cell responses in genetically diverse populations infected with different viral variants. The work is based on collecting and identifying T cell responses in well characterized patient cohorts from which we conduct genetic typing of the viral population and the patient’s human leukocyte antigen (HLA) class I and II haplotypes (Figure 1). This, the genetic information of the virus and the host, is essential for our evaluation of HLA – epitope – TCR specific interactions in relation to different aspects of the of pathogen- and malignancy-specific T cell subpopulations in blood and tissue. Our approach has important implications for our potential to identify correlates for the efficacy of virus-specific T cell responses in relation to human health.
Research group leader
Annika KarlssonSenior Researcher/Biomedical analyst
I am a group leader, teacher, Associate Professor and Deputy Head of Division at the Division of Clinical Microbiology, Department of Laboratory Medicine.
My research group is located at ANA Futura, Alfred Nobels Allé 8, KI South, Campus Flemingsberg, in close approximation with the infectious disease clinic and specialist maternity care unit at Karolinska University Hospital Huddinge
I obtained an undergraduate degree in Biomedical Laboratory Science, specializing within the field of clinical microbiology and immunology. Subsequently, I earned an PhD-degree in clinical virology from KI in 2000, followed by 4,5 years as a postdoctoral fellow at Gladstone Institutes of Virology and Immunology, UCSF, San Francisco, broadening my research expertise in clinical immunology, virus-host interactions, especially virus-specific T cell responses and how genetic variability and activity of the virus and host shapes the responding T cell population. I was appointed Associate Professor in clinical virology at Karolinska Institutet in 2009. The research conducted in my group is currently funded by several national grants received from the Swedish Research Council, Centrum for Innovative Medicine, KI Research Foundation Grants, KI Partial funding of new postgraduate student, ALF Med, and The Swedish Physicians Against AIDS Research Foundation.
The link between immune response and health in treated HIV-infection
Chronic infection and immunosuppression are important risk factors for many types of cancer. HIV is one chronic infection associated with severe immunosuppression that is only partly reversed by antiretroviral treatment (ART). In an era where HIV-infected individuals require life-long ART to control viral replication it is important to reveal the mechanisms linked to adverse health effects in order to refine therapeutic interventions, especially in pregnant women, children and adolescence. The CD4 and CD8 T cells which is an important part of the adaptive cellular immune system in both cancer and chronic infection becomes highly dysfunctional during an HIV-infection. This process is usually known as T cell exhaustion. In our projects the goal is to gain insights into how to achieve optimized treatment of HIV in perinatally infected children, pregnant women, adults, and in HIV-associated cancers. Thereby leading the way to better clinical outcomes in HIV infected and uninfected patients.
T cell immunity during pregnancy and childhood in relation to viral infection, treatment, and health
ART is necessary during pregnancy and childbirth to prevent HIV mother-to-child transmission (MTCT). Still, 20% of HIV-positive pregnant women in Sweden are not undergoing ART during the first trimester as their HIV status remained unidentified. The combined effect of modern ART and HIV during pregnancy and childhood in relation to T cell immunity, clinical, and obstetrical outcome data, with known effects on morbidity and mortality remains largely unknown (Figure 2). In this collaborative effort between the Karolinska University Hospital, Huddinge, and KI Campus Huddinge we will identify clinical, immunological, and virological factors with implications for health of pregnant women and children (Figure 3). Knowledge acquired through our study can subsequently be used as a standard when evaluating T cell immunity in pregnant women and children in relation to viral infection (i.e., effect on viral pathogenesis), new antiviral treatment strategies, following vaccination, and heath outcome.
The role of cross-reactivity and immune evasion in the control of COVID-19
Our overall goal is to understand the role of SARS-CoV-2-specific CD4 and CD8 memory T cell responses in relation to previous exposure to seasonal human coronaviruses (HCoVs), pathogenic viral SARS-CoV-2 variants, and vaccination (Figure 4). Subsequently, based on the level of viral conservation within a targeted epitope we should be able to predict how effective such immune response, naturally or vaccine induced, would be in targeting specific viral variants.
The role of virus-specific T cell exhaustion in human cancer
HIV is together with human papillomavirus (HPV), Hepatitis B and C viruses (HBV and HCV), and Helicobacter pylori (H. pylori) among the chronic infections related to cancer. In 2012 approximately 195,000 of new cancer cases in Europe were related to chronic infections. Immunosuppression is an important risk factor for many types of cancer. To increase the survival rate in invasive cancer novel immune-based treatment options needs to be developed. To obtain more efficient therapy options for cancer in different stages of development, combinational therapies using immune checkpoints inhibitors to enhance antigen-specific T cell responses are a promising option. Our research goal is to combine clinical, immunological, and molecular biology methodology with bioinformatics to characterize the molecular mechanisms of HIV- and HPV-specific T cells in human cancer affecting disease progression and health (Figure 5). Through the study-outline we will gain mechanistic knowledge of viral- and malignancy-specific T cell exhaustion that can be applied in a variety of cancers where immunomodulation can be used to counteract cancer progression.
Carina Pérez, 2011
Carina defended her PhD in 2011. Part of her doctoral research was carried out a Gladstone Institutes, University of California, San Francisco together with Prof Douglas Nixon. After her graduation, Carina started up the non-profit company DANSPIRATION in which she through dance aim to inspire, communicate, inform and integrate. Today, Carina is the head of Biosafety at Vironova AB, Stockholm, Sweden.
Melissa Norström, 2012
Melissa defended her PhD in 2012. Part of her doctoral research was carried out at Department of Pathology of the University of Florida College of Medicine together with Prof Marco Salemi. After this she continued as a postdoctoral fellow at Centre for Allogeneic Stem Cell Transplantation (CAST), Department of Oncology and Pathology, KI, Stockholm, Sweden.
Marcus defended his PhD in 2014. He was awarded the Sven Gards stipendium for the best PhD thesis in virologi at KI during 2014. He also received international postdoc grant from the Swedish research council 2014 and joined Dr. Michael Betts lab, Department of Microbiology, University of Pennsylvania, PA, USA. In 2017 he returned to KI, Department of Medicine as an Assistant Professor and became group leader in 2019 https://orcid.org/0000-0003-0633-1719.
Johanna Taurianen, 2016
Johanna defended her PhD in 2016. Since then she has continued her studies on viral-associated CD8 and NK cell responses as a Postdoctoral Fellow in Dr. Jonas Klingström group, Department of Medicine, Center for Infectious Medicine – CIM, Karolinska Institutet.
Lydia defended her PhD in 2020. After graduation Lydia continued her research path as a Postdoctoral Fellow in Group Davide Angeletti, Department of Microbiology and Immunology, University of Gothenburg, Sweden. Lydia is currently investigating B cell responses to COVID19 after infection and vaccination
2013: Karin Sundström, PhD student, MTC, Karolinska Institute, Stockholm.
2012: Charlotte Hedskog, MTC, Karolinska Institute, Stockholm
2010: Annica Lindqvist. PhD student, Karolinska Institute, Stockholm
2009: Andreas Boberg, PhD student, MTC, Karolinska Institute, Stockholm
Leda Parham, 2013
Leda defended her licentiate in 2013. She was part of a SIDA supported collaborative project between Karolinska Institutet and University of Honduras headed by me. Today she is working as a teacher and staff scientist at the Department of microbiology, University of Honduras.
2002: Piotr Nowak. University of Warszawa, Poland, included in the Karolinska Institute Research Training program (KIRT).
Annika C Karlsson
Karolinska Institutet, ANA FUTURA,
Division of Clinical Microbiology, Department of Laboratory Medicine
Alfred Nobels Allé 8
141 52 Huddinge
Ancestral SARS-CoV-2-specific T cells cross-recognize the Omicron variant.
Gao Y, Cai C, Grifoni A, Müller TR, Niessl J, Olofsson A, Humbert M, Hansson L, Österborg A, Bergman P, Chen P, Olsson A, Sandberg JK, Weiskopf D, Price DA, Ljunggren HG, Karlsson AC, Sette A, Aleman S, Buggert M
Nat Med 2022 03;28(3):472-476
Identification of resident memory CD8+ T cells with functional specificity for SARS-CoV-2 in unexposed oropharyngeal lymphoid tissue.
Niessl J, Sekine T, Lange J, Konya V, Forkel M, Maric J, Rao A, Mazzurana L, Kokkinou E, Weigel W, Llewellyn-Lacey S, Hodcroft EB, Karlsson AC, Fehrm J, Sundman J, Price DA, Mjösberg J, Friberg D, Buggert M
Sci Immunol 2021 Oct;6(64):eabk0894
Delayed expression of PD1 and TIGIT on HIV-specific CD8 T-cells in untreated HLA-B*57:01 individuals followed from early infection.
Scharf L, Tauriainen J, Buggert M, Hartogensis W, Nolan DJ, Deeks SG, et al
J. Virol. 2020 Apr;():
The known unknowns of T cell immunity to COVID-19.
Karlsson AC, Humbert M, Buggert M
Sci Immunol 2020 Nov;5(53):
Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease.
Buggert M, Nguyen S, McLane LM, Steblyanko M, Anikeeva N, Paquin-Proulx D, et al
PLoS Pathog. 2018 04;14(4):e1006973
Perturbed CD8+ T cell TIGIT/CD226/PVR axis despite early initiation of antiretroviral treatment in HIV infected individuals.
Tauriainen J, Scharf L, Frederiksen J, Naji A, Ljunggren HG, Sönnerborg A, et al
Sci Rep 2017 01;7():40354
Multidimensional Clusters of CD4+ T Cell Dysfunction Are Primarily Associated with the CD4/CD8 Ratio in Chronic HIV Infection.
Frederiksen J, Buggert M, Noyan K, Nowak P, Sönnerborg A, Lund O, Karlsson AC
PLoS One 2015 ;10(9):e0137635
T-bet and Eomes are differentially linked to the exhausted phenotype of CD8+ T cells in HIV infection.
Buggert M, Tauriainen J, Yamamoto T, Frederiksen J, Ivarsson MA, Michaëlsson J, et al
PLoS Pathog. 2014 Jul;10(7):e1004251
Multiparametric bioinformatics distinguish the CD4/CD8 ratio as a suitable laboratory predictor of combined T cell pathogenesis in HIV infection.
Buggert M, Frederiksen J, Noyan K, Svärd J, Barqasho B, Sönnerborg A, et al
J. Immunol. 2014 Mar;192(5):2099-108