Challenges the clonal selection model as this does not kill semi-allogenic foetus.
1 progenitor gives rise to different receptors, each of single antigenic specificity, further diversity induced by rearrangement of RAG genes in thymus giving different TCRs.
T-cells which react to self antigens via their TCR are deleted in central thymic selection.
A specific antigen stimulates CD8+ cells with specific TCRs via MHCI and stimulates CD4+ cells with specific TCRs via MHCII on APC.
This stimulates the T-cell to undergo clonal expansion and gives rise to many identical cells all with this specific TCR which reacts to the antigen
Cyotokines then determine further differentiation of cell types to produce different classes of T-cells
Three theories in how it does so.
1. Placenta acts as a barrier between mother and foetus
2. Specialised MHC expression of HLA-C, HLA-E, HLA-G
- Less polymorphic therefore less chance of rejection if trophoblasts express these
- Needed because NK cells will otherwise remain activated with no HLA antigen to bind
- NK cells are inactivated via HLA-C, HLA-E, HLA-G via the CD94/NKG2A and KIR2DL receptors
- NK cells are activated via HLA-C1/2 haplotypes (as HLA-C is highly polymorphic) via the KIR2DL1/2 receptors and this is linked to termination
3. Suppression of maternal immune system
- Likely via progesterone upregulating Th2 expression, Th2 releases IL-10 which inhibits Th1 production. Therefore the antibody mediated response increases and cell mediated decreases