The QKRAA or QRRAA amino acid motif also occurs quite frequently
in pathogens which reside in the human gastro-intestinal tract including
scherichia coli, Proteus mirabilis, lactobacillus lactis, Brucellaovis
and many other anaerobic gut bacteria (3). The QKRAA or QRRAA
sequences are found specifically in a particular type of protein
contained in gut bacteria, called DnaJ proteins. DnaJ proteins
normally have a bacterial partner/ligand protein called heat shock
proteins (HSP70). It is the QKRAA or QRRAA amino acid sequence of
DnaJ which allows it to bind HSP70.
When the MHC presents endogenously derived DRB1 alleles which
contain the QKRAA or QRRAA amino acid motif, then circulating HSP70
proteins (which normally bind DnaJ proteins) can bind the body's own MHC
presented QKRAA or QRRAA sequences. Circulating CD4+ T-lymphocytes
recognize this HSP70/QRRAA sequence as foreign and mount an immune
response on all cells presenting this (HSP70) amino acid motif.
We believe that myelin basic protein contains an amino acid
equence that is homologous to an A.A. sequence found in HSP70, and it
is this three way mimicry between DRB1 peptides, bacterial peptides and
self peptides which causes self tolerance to be broken.
So, how does a paleodiet have anything to do with this process?
Paleodiets are characterized by their lack of cereal grains, legumes,
dairy products, and yeast containing foods. Both cereal grains and
legumes contain glycoproteins called lectins which bind intestinal
epithelial cells and change the permeability characteristics of these
intestinal cells (4,5). Not only do these lectins cause an increase =
of
the translocation of gut bacteria to the peripheracy, they cause an
increased overgrowth of gut bacteria as well as a change in the gut
flora (4,5). Further, cereal and legume derived lectins (WGA, PHA
respectively) cause increased expression of intracellular adhesion
molecules (ICAM) in lymphocytes (6) which allow bacterial/immune
complexes to move from gut to the affected tissue. Additionally,
cereal and legume lectins increase lymphocytic expression of common
inflammatory cytokines such as tumor necrosis factor alpha (TNFa),
interleukin 1 (IL-1) and IL-6 which are known promoters of autoimmune
disease.
The cell walls of cereals and legumes contain a storage protein,
GRP 180, which also can act as a ligand to self presented MHC peptides
(7). Further, peptides contained in dairy proteins (bovine serum
albumins - BSA, among many) also may contain peptide sequences which can
interact with endogenously presented peptides (8). Cereal, legume,
>dairy and yeast free diets potentially have therapeutic benefit in many
autoimmune related disorders via their ability to reduce gut
permeability and decrease the exogenous antigenic load both from
pathogenic bacteria and from potentially self mimicking dietary
peptides.
REFERENCES
1. Singh VK et al. Antibodies to myelin basic protein in children
with autistic behavior. Brain, Behavior and Immunity 1993;7:97-103.
2. Warren RP et al. Strong association of the third hypervariable
region of HLA-DR beta 1 with autism. J Neuroimmunol 1996;67:97-102.
3. Auger I et al. A function for the QKRAA amino acid motif:
mediating binding of DnaJ to DnaK. J Clin Invest 1997;99:1818-22.
4. Liener IE. Nutritional significance of lectins in the diet.
In: The Lectins: Properties, Functions, and Applications in Biology and
Medicine. IE Liener (Ed), Academic Press, Orlando, pp 527-52.
5. Pusztai A. Dietary lectins are metabolic signals for the gut
and modulate immune and hormone functions. Eur J Clin Nutr
1993;47:691-99.
6. Koch AE et al. Soluble intercellular adhesion molecule-1 in
arthritis. Clin Immuunol Immunopathol 1994;71:208-15.
7. Dybwad A et al. Increases serum and synovial fluid antibodies
to immunoselected peptides in patients with rheumatoid arthritis. Ann
Rhem Dis 1996;55:437-41.
8. Perez-Maceda B et a. Antibodies to dietary antigens in
rheumatoid arthritis--possibel molecular mimicry mechanism. Clin Chim
Acta 1991;203:153-65. =09
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End of PALEODIET Digest - 29 Mar 1998 to 30 Mar 1998 (#1998-16)
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