Journal of Mosquito Research, 2013, Vol.3, No.1, 1-10
ISSN 1927-646X
http://jmr.sophiapublisher.com
2
associated with the development of DENV
pathogenesis (Furuta et al., 2012). Interestingly,
several human immunities are controlled by the
expression of human leukocyte antigen (HLA) and
expression of HLA molecules are increased in DENV
infection (Lan et al., 2008; Lan and Hirayama, 2011).
HLA allele polymorphisms have correlation with T
cell differentiation profile and it will determine the
variation of viral infection response (Lan and
Hirayama, 2011). Several studies have shown a
correlation between HLA and DENV infection. Sierra
et al (2007) found that amino acid peptides on poly
DENV protein bind to HLA class I and class
?
allotype have a correlation with susceptibility and
protection against DENV infection. Study conducted
by Apanna et al (2010) also documented that HLA
class I and class
?
had association with
susceptibility and protection of DENV infection. HLA
also linked to development of dengue diseases
pathogenesis. Lan et al (2008) found a correlation
between HLA class I and
?
and DENV infection
development. Study conducted by Azeredo et al (2010)
also found that certain types of HLA genes are found
in patients with DSS. In addition, study about
association of HLA and response to vaccination has
been reported (Poland et al., 2008). Therefore, this
paper will discuss about the association of HLA and
HLA-related protein gene polymorphisms with
susceptibility, severity, and protection against DENV
infection in brief view setting.
2.
Discussion
The role of HLA in the immune system is to help the
immune system to distinguish body protein with
foreign protein, such as viruses and bacteria (Panchal
et al., 2012). It displays peptide antigens to T
lymphocytes resulting in introduction of elements and
triggers an immune response (Lan and Hirayama,
2011).
HLA system consists of a variety of genes, play
important roles in human immune system. HLA is
encoded by the major histocompatibility complex
(
MHC), located on chromosome 6p21 consisting of
approximately 0.5% (>150) protein coding genes
(
Appanna et al., 2010; Xie et al., 2010; Wagenaar et
al., 2004). HLA region is divided to two classical
regions, class I (HLA-A, B, C) and class
?
(
HLA-DR, DQ, and DP) and an intervention region
(
class
?
) (
Xie et al., 2010). Genes encoding HLA
class I and class
?
are the most polymorphic
genomes in humans (Lan and Hirayama, 2011).
2.1
HLA class I
HLA class I gene encodes polypeptide a chain of HLA
class I molecules; whereas the ß chain of HLA class I
is encoded by beta2-microglobulin, a gene located on
chromosome 15. a chain of HLA class I has 5 domain:
2
peptide-binding domain (a1 and a2), 1
immunoglobulin-like domain (a
3
),
transmembrane
region, and cytoplasmic tail. HLA region consists of
approximately 200 HLA class I genes, but the most
important HLA in the immunity is HLA-A, HLA-B,
and HLA-C. HLA class I is expressed on all somatic
cells and platelet although the levels of expression
depend on their respective networks (Klein and Sato,
2000).
a1 and a2 domain contain various amino acid
sequences, and determine the HLA class I antigenic
specificity molecules. a3 and ß2m domains together
form a immunoglobulin constant like-fold. Light
chains a1 and a2 domain form a structure consisting
of eight ß strands and two a helix antipararel that have
a role as antigen peptides binding site (Choo, 2007).
Several studies have identified HLA alleles associated
with DENV infection susceptibility and severity such
as A*0207, A*1, A*2, A*24, A*31, B blank, B*13,
B*40, B*46, B*51, B*52, B*53, and B*57
(
Chaturvedi et al., 2006; Panchal et al., 2012;
Wagenaar et al., 2004). Whereas some HLA alleles
such as A*0203, A*03, A*29, A*33, B*13, B*14,
B*15, B*18, B*44, B*49, B*52, B*62, and B*76,
B*77 are associated with protection of DENV
infection (Chaturvedi et al., 2006; Panchal et al., 2012;
Wagenaar et al., 2004). See Table 1.
The associations between MHC class I and CD8
+
have
an important role in the process of DENV infection.
MHC class I molecule will bind to the protein
fragments or endogenous peptide and interact with
CD8
+
.
Furthermore CD8
+
represents antigen-specific
and responds to destroy infected cells. All cells in the
human body that express MHC class I molecules can
be the targets of CD8
+
.
The role of CD8
+
in the
infection process is to monitor all cells in the body and