Abstract
The human leukocyte antigen system (HLA) is a cluster of highly polymorphic genes essential for the proper function of the immune system, and it has been associated with a wide range of diseases. HLA class I molecules present intracellular host- and pathogen-derived peptides to effector cells of the immune system, inducing immune tolerance in healthy conditions or triggering effective immune responses in pathological situations. HLA-C is the most recently evolved HLA class I molecule, only present in humans and great apes. Differentiating from its older siblings, HLA-A and HLA-B, HLA-C exhibits distinctive features in its expression and interaction partners. HLA-C serves as a natural ligand for multiple members of the killer-cell immunoglobulin-like receptor (KIR) family, which are predominately expressed by natural killer (NK) cells. NK cells are crucial for the early control of viral infections and accumulating evidence indicates that interactions between HLA-C and its respective KIR receptors determine the outcome and progression of viral infections. In this review, we focus on the unique role of HLA-C in regulating NK cell functions and its consequences in the setting of viral infections.
Highlights
The human leukocyte antigen (HLA) system represents a cluster of highly polymorphic genes that are associated with a large number of diseases
We focus on the unique role of HLA-C in regulating natural killer (NK) cell functions and its consequences in the setting of viral infections
Its unique role is further highlighted by the rapid co-evolution of HLA-C recognizing killer-cell immunoglobulin-like receptor (KIR) since its first appearance
Summary
The human leukocyte antigen (HLA) system represents a cluster of highly polymorphic genes that are associated with a large number of diseases. Besides peptide specificity and binding affinity, the expression level on the cell surface is an important factor for an effective immune response. An SNP (rs2395471) in the OCT1 transcription factor binding site, located ∼800 bp upstream the HLA-C transcription start side, is significantly associated with HLA-C expression levels. -B, exhibits regulatory elements away from transcription initiation is associated with differences in HLA-C expression that lead a lower cell surface expression.is the binding of microRNAs (miRNAs) to spelevels. Variations in exon 2 and 3, encoding the peptide-binding site domains, contribute to differential cell surface expression. Transcription factors for W/S are still unknown, but X1 has binding sites for RFX and ETS, X2 has binding sites for CREB results in reduced transcript levels and lower HLA-C expression, which increases NK cell and ATF1 and Y for NFY.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
