Research Topic

Role of HLA and KIR in viral infections

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Both T lymphocytes and Natural Killer (NK) cells are important for control of viral infections, including chronic viral infections like HIV, HCV and CMV, but also resolving infections such as influenza virus infection. Human leukocyte antigen (HLA) class I molecules are important in guiding T-cell responses ...

Both T lymphocytes and Natural Killer (NK) cells are important for control of viral infections, including chronic viral infections like HIV, HCV and CMV, but also resolving infections such as influenza virus infection. Human leukocyte antigen (HLA) class I molecules are important in guiding T-cell responses by presenting small virus-derived peptides to T cells, that will react by proliferation and effector function after recognition by the T cell receptor (TCR). Additionally, HLA molecules expressed on target cells are ligands for a number of surface receptors on NK cells, including activating and inhibitory killer cell immunoglobulin-like receptors (KIRs). As both HLA and KIR molecules are highly polymorphic, each individual host is able to mount a unique immune response. The array of virus-derived peptides presented by HLA molecules determines the height, strength and immunodominance of a T-cell response. In addition, the HLA background of an individual plays a role in immune evasion thereby contributing to viral variation and influencing viral fitness.

KIRs play an essential role in the regulation of NK activity, allowing NK cells to sense and respond to HLA class I downregulation, a major mechanism for viruses and tumors to escape T cell control. Although NK-cell mediated immunity can contribute to viral control and clearance during the initial acute phase of these infections, extensive activation of NK cells during acute infection and persistent stimulation during chronic infection might contribute to virus-associated pathology. Increasing insight is gained in the function of cells expressing specific KIRs. As KIRs exhibit substantial genetic diversity, there is significant variation in the NK cell repertoire between individuals and between populations. Together with the highly diverse HLA locus, this leads to a multitude of possible KIR:HLA combinations.

There is increasing evidence from epidemiological and functional studies that NK cells may play an important role in the early response to viral infections, through killing of virus-infected cells and modulation of adaptive immunity. The mechanisms how NK cells contribute to the establishment of a strong and effective adaptive immune response are beginning to unravel and understanding the impact of interplay between NK and other immune cells, such as dendritic cells (DCs) and CD4+ T cells, to shape adaptive T-cell responses has become an important research focus.

In this research topic we aim to provide insight in the latest aspects of NK cell and T-cell immunity to viruses, and their interaction, focusing on the role of specific HLA-molecules and KIR alleles. Strong HLA-associations have been found in the past decades for a number of infectious diseases and similar associations with KIR molecules are becoming apparent. The effect of these associations on specific immune responses and the interplay between HLA and KIR molecules is an emerging research area.


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