VIEWING AIDS FROM A GLYCOBIOLOGICAL PERSPECTIVE - POTENTIAL LINKAGES TO THE HUMAN FETOEMBRYONIC DEFENSE SYSTEM HYPOTHESIS

are very poorly understood, as are the mechanisms underlying the prote ction of the developing human from the maternal immune response. Recen t data suggests that the human immunodeficiency virus (HIV) may be usi ng the glycosylation system of the T lymphocytes to acquire glycans fo r its glycoproteins that enable it to disrupt carbohydrate dependent i mmune cell interactions or induce aberrant immune reactions. Consisten t with this hypothesis, gp120 from HIV infected human H9 lymphoblastoi d cells expresses biantennary N-linked glycans with a bisecting GlcNAc sequence on 11% of their total oligosaccharides. This specific carboh ydrate sequence has recently been shown to protect K562 erythroleukemi c 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 it is also express ed on human spermatozoa. Thus both the human gametes and HIV produced by H9 cells carry this same protective carbohydrate epitope on their o uter surfaces. Human alpha-fetoprotein expressed in the developing hum an also carries the bisecting GlcNAc sequence, indicating that it may be suppressing the emerging fetal immune response by using its carbohy drate sequence as a functional group. We have suggested that the devel oping human and the gametes are also protected by soluble immunosuppre ssive glycoproteins found in the amniotic fluid and seminal plasma kno wn as glycodelin-A (GdA) and glycodelin-S (GdS) respectively. Structur al analysis of their N-linked oligosaccharides combined with other fun ctional studies suggest that GdA and GdS employ their very unusual car bohydrate sequences as functional groups that enable them to manifest their Immunosuppressive activities. GdA and GdS are significant compon ents of our recently proposed model for the protection of the developi ng human and gametes designated the human fetoembryonic defence system hypothesis. A striking relationship now emerging is that the same unu sual carbohydrate sequences associated with these immunosuppressive gl ycodelins 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 t wo new corollaries should be added to our recently proposed defence sy stem hypothesis: (i) mimicry or acquisition of glycans that are used i n this protective system by pathogens or tumour cells may enable them to either subvert or misdirect the human immune response, thereby grea tly increasing their pathogenicity; and (ii) expression of glycoconjug ates used in this system by normal cells and tissues outside the repro ductive system may protect them from immune responses, especially in t hose cases where major histocompatibility recognition is either absent or minimal. A better understanding of this hypothesis and its corolla ries may enable us to address the molecular mechanisms underlying not only AIDS but also a host of other very serious pathological condition s in the human.