Molecular Human Reproduction, Vol 3, 5-13, Copyright © 1997 by Oxford University Press
GF Clark, A Dell, HR Morris, M Patankar, S Oehninger and M Seppala
The primary molecular changes that lead to development of acquired
immunodeficiency syndrome (AIDS) are very poorly understood, as are the
mechanisms underlying the protection of the developing human from the
maternal immune response. Recent data that the human immunodeficiency virus
(HIV) may be using the glycosylation system of the T lymphocytes to acquire
glycans for its glycoproteins that enable it to disrupt carbohydrate
dependent immune cell interactions or induce aberrant immune reactions.
Consistent with this hypothesis, gp120 from HIV infected human H9
lymphoblastoid cells expresses biantennary N-linked glycans with a
bisecting GlcNAc sequence on 11% of their total oligosaccharides. This
specific carbohydrate sequence has recently been shown to protect K562
erythroleukemic cells from natural killer (NK) cell responses when
presented on the cell surface. We have recently demonstrated that bisecting
biantennary type N-linked glycans are also expressed on the human zona
pellucida (ZP); previous lectin binding studies indicate that is also
expressed on human spermatozoa. Thus both the human gametes and HIV
produced by H9 cells carry this same protective carbohydrate epitope on
their outer surfaces. Human alpha- fetoprotein expressed in the developing
human also carries the bisecting GlcNAc sequence, indicating that it may be
suppressing the emerging fetal immune response by using its carbohydrate
sequence as a functional group. We have suggested that the developing human
and the gametes are also protected by soluble immunosuppressive
glycoproteins found in the amniotic fluid and seminal plasma known as
glycodelin-A (GdA) and glycodelin-S (GdS) respectively. Structural analysis
of their N-linked oligosaccharides combined with other functional studies
suggest that GdA and GdS employ their very unusual carbohydrate sequences
as functional groups that enable them to manifest their immunosuppressive
activities. GdA and GdS are significant components of our recently proposed
model for the protection of the developing human and gametes designated the
human fetoembryonic defence system hypothesis. A striking relationship now
emerging is that the same unusual carbohydrate sequences associated with
these immunosuppressive glycodelins are also specifically expressed on
intravascular helminthic parasites, Helicobacter pylori, human tumour
cells, and HIV infected T lymphocytes. The information presented in this
review suggests that two new corollaries should be added to our recently
proposed defence system hypothesis: (i) mimicry or acquisition of glycans
that are used in this protective system by pathogens or tumour cells may
enable them to either subvert or misdirect the human immune response,
thereby greatly increasing their pathogenicity; and (ii) expression of
glycoproteins used in this system by normal cells and tissues outside the
reproductive system may protect them from immune responses, especially in
those cases where major histocompatibility recognition is either absent or
minimal. A better understanding of this hypothesis and its corollaries may
enable us to address the molecular mechanisms underlying not only AIDS but
also a host of other very serious pathological conditions in the human.
REVIEW, TUTORIAL
Viewing AIDS from a glycobiological perspective: potential linkages to the human fetoembryonic defence system hypothesis
Department of Biochemistry, Eastern Virginia Medical School, Norfolk 23501-1980, USA.
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