Journal of Mosquito Research, 2013, Vol.3, No.1, 1-10
ISSN 1927-646X
http://jmr.sophiapublisher.com
4
T lymphocytes CD4
+
and CD8
+
cells have important
role in DENV infection pathogenesis (Kurane et al.,
2011).
T cells reactive against DENV mediate DHF
pathogenesis through endothelium cell apoptosis and
induce cytokine secretion that results in increased
vascular permeability. CD4
+
has an important role
against infection, such as antibody response maturisation,
macrophage activation, increase natural killer (NK)
cell activity, and antibody switching. The relationship
between CD4
+
and MHC class
?
has an important
role in controlling the infection process. Activated
CD4
+
recognizes antigen presented by MHC class
?
.
Furthermore CD4
+
releases cytokines in response to
antigen stimulation and also capable of lysing infected
cells (Chaturvedi et al., 2006; Rothman, 2011).
In DENV infection, CTL has an important role to
recognize DENV epitopes. DENV epitopes involved
in this process is nonstructural protein (NS). It is the
bifungsional protein that controls serine protease and
nucleic acid activity. Protease is an important part for
virus life cycle (Chaturvedi et al., 2006). The epitopes
recognized by DEN-specific are located in most of the
structural and non-structural proteins, but NS3 is the
protein that is most dominantly recognized (Kurane et
al., 2011). There are several CTLs, however only
JK34, JK15, JK44, JK5, JK4, JK43, JK10, JK39,
JK28, and JK26 that have important role in DENV
infection process (Chaturvedi et al., 2006; Okamoto et
al., 1998). CD4
+
and CD8
+
recognize NS3 of DENV
through JK34. NS3 recognizing through JK34 is
mediated by the HLA-DPw2 restriction. NS3
recognizing through JK4 and JK43 is mediated by
HLA-DR15 allele restriction. NS3 recognition process
occurs very specific. Several CTL involved in NS
recognizing, such as JK15 recognizes DV3 NS3, JK44
recognizes DV1 and DV2 NS3, and JK5 recognizes
DV1 and DV3 NS3. This recognition process involves
not only one epitope (NS3), but also NS1 and NS2a
(
Chaturvedi et al., 2006).
The correlation of HLA class
?
genes with both
enhanced and decreased susceptibility to DHF has
been reported. Several studies have reported the
association of DHF with HLA class
?
antigens.
Fernández-Mestre et al (2009) analyzed the frequency
of HLA class I (-A, -B and –C) and class
?
(-
DRB1)
polymorphisms in DF and DHF patients, and its
relationship with clinical manifestations of disease in
Venezuelan. In patients with DENV infection,
DRB1*02 and DRB1*03 decreased significantly
compared with healthy individuals. It suggested that
these allele groups could be associated with
diminished infection susceptibility. Among DF
patients there was a significant increase of DRB1*15
compared with healthy individuals. It suggested that
this allele could be associated with infection
susceptibility. Another study conducted in Mexican
found that HLA-DRB1 played as protective allele in
the patients with DENV infection compared to healthy
individuals. It suggest that class
?
MHC antigens
probably process and present immunological
determinants of protein E (envelope protein of DENV)
and HLA-DRB1*04 may present these viral antigens
to CD4+ lymphocytes leading immune response
activation and consequently protected from DHF
(
LaFleur et al., 2002). A study conducted in Southern
found that HLA-DRB1*0901 decreased significantly
in patients with DSS compared to control and HLA-
DRB1*0901 decreased significantly in DSS compared
with DHF (Lan et al., 2008). Other study found
HLA-DRBI*04 and HLA-DRBI*07 were protective
alleles to DENV infection (Sierra et al., 2007).
Several HLA class
?
members are associated with
susceptibility to dengue infection. Recently, Malavige
et al (2011) compared DRB1*08 and DRB1*12 alleles
in 110 DHF patients and 119 control individuals. It
showed that the frequency of DRB1*08 allele was
28.7
times higher in DSS patients than in normal
population and HLA-DRB1*12 was higher in primary
DENV infection compared with control. A Study
conducted by Falcón-Lezama et al (2009) found
HLA-DQB1*0202 was positively associated with DF
only. It concluded that HLA-DQB1 alleles have
association with the risk of symptomatic disease
development, DF and DHF. Furthermore, a study
conducted in Southern Brazilian population showed
that HLA-DQ1 was found to be susceptibility alleles
to patients with DENV infection (Polizel et al., 2004).
2.3
HLA class
?
HLA class
?
genes do not code for HLA molecules.
HLA class
?
consists of complement components (C2,