Research focus for Annika Karlsson group

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 (Figure 1). We are the link between immune response and health with an empahsize on HIV and SARS-CoV-2 infection.

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 – T cell receptor (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. Our goal is to guide future treatments and vaccinations strategies in children and elderly by increase our understanding of the cellular prerequisites for development, maintenance, and function of antiviral memory T cells.

Research genre image showing Figure 1. Dissecting antiviral T cell immunity in relation to age, pregnancy, viral infections, cancer, treatment, and clinical health.
Figure 1. Dissecting antiviral T cell immunity in relation to age, pregnancy, viral infections, cancer, treatment, and clinical health. Photo: Annika Karlsson


1. 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 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 (Figure 2). 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.

Genre image showing The importance of T cells in the battle against viral infection and cancer.
Figure 2. The importance of T cells in the battle against viral infection and cancer. During the induction of an antigen-specific T cell response. The HLA-I-peptide complex is recognized by the CD8 T cells while peptides presented by HLA-II are recognized by CD4 T cells. The ability of the host to generate efficient T cell responses are dependent on the epitopes targeted, antigen abundance, and host genetic factors such as HLA type and TCR repertoire. CD4 T cells coordinate immunity and CD8 T cells exert antiviral effector functions. During cancer or a chronic infection, the immune system is not able to clear the antigen, persistent antigen stimulation. Subsequently, the memory T cell repertoire becomes highly dysfunctional. This process is known as T cell exhaustion. Photo: Annika Karlsson

2. T cell immunity during pregnancy and childhood in relation to viral infection, treatment, and health

The severity and clinical profile of many viral infections is affected by age and pregnancy. Studies on qualitative aspects of antiviral cellular immunity in children and pregnant women is outdated calling for new insights into their role for health and immunopathogenesis. Qualitative differences in viral-specific T cell responses may reflect the ability of the host to control virus infections and respond to vaccination.  Pregnancy presents a major challenge for the immune system, where foetal immune tolerance must be upheld while maintaining immune functions. While pregnancy does not increase general susceptibility to infection, it has been shown to increase the risk of severe disease to viral infections (HIV, Coronavirus, Influenza). In this collaborative effort we aim to define T cell immunity in relation to clinical, virological, and bacteriological factors in HIV-infected and HIV uninfected children, pregnant women and their offspring (Figure 1). Our results will provide a rational framework for personalized monitoring and evaluation of antiviral treatment and vaccination strategies for children and pregnant women.

3. The role of cross-reactivity and immune evasion in the control of respiratory viral infections

Our current understanding of T cell immunity against respiratory virus and their viral variants in relation to age is incompletely characterized (Karlsson AC, Sci Immunol. 2020). Infants and young children and elderly are more vulnerable to severe viral infections, particularly to respiratory and enteric viruses, including Coronaviruses (SARS-CoV-2 and the four circulating seasonal coronaviruses), Influenza viruses, and Respiratory syncytial virus, compared to adults. We will provide the scientific community with fingerprints of the memory T cell responses against these common respiratory tract viral infections from childhood until late adulthood (Humbert M, PNAS. 2023). 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 1). 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.

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4. The role of virus-specific T cell exhaustion in human cancer

Chronic antigenic stimulation, such as by cancer or viral antigens, invariantly causes T cell exhaustion. 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. T cell exhaustion and 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 1). 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.

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