چکیده
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Abstract
Host genetic factors play a central role in determining the clinical phenotype of
human diseases. Association between two polymorphic loci in human genome,
human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptors
(KIRs), and genetically complex infectious disease particularly those of viral
etiology have been historically elusive. Hence, defining the influence of genetic
diversity in HLA and KIRs on outcome of viral infection has begun extensively in
clinically well-defined cohort studies. HLA genes encode molecules which present
antigenic peptide fragments to T lymphocytes as central players in adaptive
immunity against infectious diseases. KIRs are expressed on natural killer cells
which perform a vital role in innate immunity to pathogen infection. The effector
function of NK cells such as direct killing of infected cells, cytokine production
and cross-talk with adaptive immune system are dependent on activation of NK
cells which is determined by its surface receptors. Among these receptors, KIRs
which interact with HLA class I are mainly inhibitory and exhibit substantial
genetic diversity. An extensive body of association studies indicates a role for
HLA–KIRs interactions in infectious diseases, autoimmune disorders, cancer,
transplantation and reproduction. Various compound HLA-KIR genotypes appear
to affect outcome of viral infections that suggests a role for HLA class I diversity
in innate immunity as well as adaptive immune responses. The aim of this review
is focusing on the impact of HLA and KIR alleles and different combinations of
these alleles on clinical outcome of viral diseases to validate this proof-of-concept
with respect to the therapeutic interventions.
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