Unsaturated fatty acids are potent MHC-II loading enhancers (MLE)

Small molecules that enhance the binding of antigens to MHC-II molecules are (MHC-loading enhancers, MLE) may be involved in the pathophysiology of autoimmune diseases. They may also be relevant to potentiate the efficacy of vaccines and immunotherapeuticals [1].

We recently reported on the MLE activity of terpenoids as well as acetylenic spiroethers from essential oils [2].

In search for further polyynes with MLE activity we have now investigated the CH₂Cl₂ extracts of underground parts of the Apiaceae Foeniculum vulgare var. azoricum (Fennel), Pastinaca sativa ssp. sativa (Parsnip) and Apium graveolens var. rapaceum. (Celery), which displayed interesting results in our test system (Dissociation-enhanced fluorescent immunoassay measuring loading of soluble MHC-II (HLA-DR1) with an influenza HA peptide in comparison with the positive control Adamantylethanol [1, 2]).

Bioassay-directed fractionation of the root extracts showed the highest activity in fractions containing unsaturated fatty acids (FA). LC/MS and NMR analyses revealed linoleic acid (LA) as constituent in the most active fractions. Consequently, a variety of natural FA were tested for MLE activity (Table 1). Overall, ALA was the most active FA (Fig. 1). Other unsaturated FA were markedly less active. Saturated FA did not show any MLE activity. Moreover, Linseed oil, rich in ALA, was inactive. The free acid hence must be the active principle directly responsible for MLE activity.

The finding that particular unsaturated FA, important constituents of daily nutrition possess a specific MLE effect represents a novel aspect regarding their physiological importance. These FA – besides nutritional value and involvement in homeostasis, membrane integrity and mediator synthesis – may thus also be involved in processes directly related to antigen presentation and immunity.

Tab. 1: n-fold increases of the absolute MLE-activity of fatty acids in comparison to 1-Adamantylethanol

Unsaturated fatty acid	n at c = 0.01%	n at c = 0.002%
Oleic acid	26.7	18.2
α-Linolenic acid	56.1	22.3
γ-Linolenic acid	37.9	18.6
Arachidonic acid	12.7	8.0
Ricinoleic acid	21.9	9.7
1-Adamantylethanol*	71	6.5
Linoleic acid	18.3	11.4
1-Adamantylethanol*	37.9	4.1
*Positive control measurements of two independent experimental series

Fig. 1: MLE-activity of fatty acids in relation to the control 1-Adamantylethanol

References:

[1] Höppner S et al., 2006. J. Biol. Chem. 281: 38535 – 42.

[2] Schnieders A et al., 2011, Planta Med. 77, PM174