Biology Reference
In-Depth Information
viral nucleic acid in endosomes).
76
With nematodes, there are several
candidates for chemical PAMPs that are also not found in mammals, such
as cuticulin proteins, ascarosides, and a plethora of protein structures
(such as the NPAs) that are unknown beyond nematodes, and there is
already some evidence of unusual TLR stimulation activity by certain
specialized nematode molecules.
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THE STRUCTURE AND FUNCTION OF THE
MAJOR ALLERGEN OF
ASCARIS
e
ABA-1
ABA-1 was first identified as a small (~14.4 kDa; 14,400 molecular
mass) protein that is particularly abundant in the pseudocoelomic fluid of
adult Ascaris, and also appears in culture fluid of the infective and lung
stage larvae.
1,24,78
It is among the antigens of the parasite that are under
strong MHC-mediated genetic control of the immune repertoire in
rodents (see above). As also detailed above, humans infected with the
parasite are heterogeneous in their immune responses to ABA-1, such that
some people respond strongly, and some not at all, despite attested
infection and strong immune responses to other components of the
parasite (
Figure 3.3
). Interest in the protein grew with the demonstration
that it is an allergen in the context of infection (i.e. that it is the target of IgE
antibody),
23,26,28,29
so could be relevant to allergic manifestations such as
Loeffler's syndrome and IgE-based immunity. Direct amino acid
sequencing of ABA-1 purified from the parasite showed that it was
unrelated to any type of protein then known.
24
When cDNA encoding
ABA-1 was isolated
25
it was found that the encoded protein was enriched
in charged amino acids (see Figure 2 of,
79
) which has been proposed as
a characteristic of allergens in general.
80,81
Whether or not ABA-1 is
intrinsically allergenic, or is only so in the context of infection, remains to
be determined, although there is evidence that its allergenicity is condi-
tional on the means by which it is presented to the immune system
e
animals immunized with the protein in Freund's adjuvant develop strong
IgG antibodies to it, but no IgE antibody.
44
Around the time that amino acid sequence information for ABA-1
began to emerge, other laboratories working on a range of nematode
parasites were focusing on an unusual class of proteins produced as large,
repetitive polyprotein precursors that are post-translationally cleaved
into multiple copies of ABA-1-like molecules.
82
e
86
Moreover, like ABA-1,
these tended to be targets for IgE antibody responses.
85
ABA-1 was also
found to be synthesized as a long, precursor polypeptide comprising
head-to-tail, tandemly repeated regions that are post-translationally
cleaved at regularly-spaced proteinase cleavage sites into about ten
small proteins of approximately 14.4 kDa.
25
Some of these repeated units
