EBV Conference 2008 Guangzhou - Baylor College of Medicine

196 (RegID: 1525)
Mainthan Palendira
Institution: Garvan Institute of Medical Research
e-mail: m.palendira@garvan.org.au
DISSECTING THE ROLE OF SAP IN ANTI-EBV RESPONSES THROUGH EXAMINATION OF
XLP CARRIERS
Palendira. U1, Hislop. A2, Rickinson. A2 and Tangye.S.G1
Posterabstract:
X-linked lymphoproliferative (XLP) disease is an inherited immunodeficiency characterised by extreme
sensitivity to Epstein Barr Virus (EBV) infection. XLP patients are typically asymptomatic prior to EBV
exposure. However, EBV induces the clinical disease in > 90% of affected individuals. In contrast to EBV
infection of healthy individuals, which is self-limiting, exposure of XLP patients to EBV induces a
vigorous and uncontrolled immune response involving polyclonally activated lymphocytes and monocytes.
Despite such immune activation, XLP patients fail to control EBV infection resulting in severe and often
fatal IM (58% of cases), hypogammaglobulinaemia (30% cases) and importantly B-cell lymphoma (35%
of cases). A number of specific defects have been identified in lymphocytes from XLP patients. These
include an impairment in cytotoxic function of CD8+ T cells and NK cells, abrogated development of
NKT cells, a deficiency in memory B cells and impaired effector function of CD4+ T cells. The gene
mutated in XLP, SH2D1A, encodes the cytoplasmic SH2-domain containing adaptor protein SAP
(SLAM-associated protein) which associates with the cytoplasmic domains of members of the SLAM
family of cell surface receptors. Due to the complications in XLP patients, it would be desirable to
examine lymphocyte function in cells that are genetically identical except for the presence or absence of
functional SH2D1A. We therefore have been studying female carriers of XLP. We have been able to detect
SAP deficient and SAP sufficient CD8+ T cells in XLP carriers. Using this model, we have been able to
identify phenotypic and functional differences between SAP+ and SAP- CD8+ T cells. We have also been
characterizing the responses to not only EBV, but also Cytomegalovirus (CMV) and Influenza in these
XLP carriers.
EBV Conference 2008 Guangzhou
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