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Introduction

The term CD4  is also referred to as cluster of differentiation 4, which is a
55-KDa single chain transmembrane glycoprotein
expressed predominantly on the surface of T helper  and other immune cell types such as monocytes,
macrophages,
and dendritic cells1, a being a distinct cellular marker on the surface of these
cells CD4 cells are lymphocytes that are component of the human immune system.
They are called helper cells because; one of their main roles, which is crucial
in achieving a regulated and effective immune response is to send signals to B
lymphocytes and other of immune cell types, including the CD8 killer cells,
which then destroys the infectious particle.2 CD4 is thus
indispensable in adaptive immunity.  Based
on its characteristic of having four Ig-like amino acid domains, CD4 is classified
as a member of the immunoglobulin superfamily. These
immunoglobulin domains (D1 to D4) are exposed on the
extracellular surface of the cell. D1 and D3 exhibit
similar structural features with immunoglobulin
variable (IgV) domains, while D2 and D4 shows
similarities to immunoglobulin constant (IgC) domains (b). The immunoglobulin
variable (IgV) domain of D1 consists of an immunoglobulin-like
?-sandwich fold with seven ?-strands in 2 ?-sheets linked by a di-sulfide bond in
a Greek key topology.3 The co-ligation of CD4 with the ?2-domain of MHC class II
molecules is done mainly through its D1 domain. Thus, T cells
displaying CD4 molecules on their surface, therefore, are specific for antigens
which are presented by MHC II and not by MHC class I,
hence they are MHC class II-restricted.
The short cytoplasmic/intracellular
tail (C) of CD4 contains a unique sequence of amino acids
that allows rapid autophosphorylation of  tyrosine
kinase Lck.
2 CD4 is a co-receptor
of the T cell receptor (TCR) and assists the latter in
communicating with antigen-presenting cells (APC). The TCR complex and CD4 each bind to
distinct regions of the antigen-presenting MHCII molecule – ?1/?1
and ?2, respectively causing the proliferation of the CD4 T cells
and their differentiation into Th1, Th2 Th17 and follicular helper cells which
mediate immune reactionsc. The signal generated by the TCR is amplified by
the Immunoreceptor tyrosine activation
motifs (ITAM) which is the tyrosine
kinase Lck bound to the cytoplasmic tail of CD4 to
tyrosine-phosphorylate as a result of the interaction between the intracellular/extracellular
CD4 and TCR2. Many molecular
components of the signaling cascade of an activated T cell and their resultant T
helper cell activation are dependent on Tyrosine
kinase Lck. T cells are also
activated via the Phosphorylated ITAM motifs on CD3 which activate SH2 domain-containing
protein tyrosine kinases (PTK) such as Zap70. This activated SH2 domain leads
to tyrosine phosphorylation further leading to transcription factor activation
such as NF-?B thereby activating the T cells 2. The interactions
of  CD4 with SPG21,4
Lck5,6,7,8,9 and Protein unc-119 homolog have all been
documented10.
 Essentially, CD4 cells acquire numerous functions
on activation. This diversity in function is essential for good health (d)

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