Fe-Cu binary alloys are often used to mimic the behaviour of reactor pressure vessel steels. Their study allows identifying some of the defects responsible for irradiation-induced hardening. But recently the influence of manganese and nickel in low-Cu steels has been found to be important as well. In contrast with existing models found in the literature, which predict that hardening saturates after a certain dose, Fe alloys containing nickel and manganese irradiated in a material test reactor (BR2) show a continuous increase of hardening, up to doses equivalent to about 40 years of operation. Considerations based on positron annihilation spectroscopy analyses suggest that the main objects causing hardening in Cu-free alloys are most probably self-interstitial clusters decorated with manganese. In low-Cu reactor pressure vessel steels and in Fe-CuMnNi alloys, the main effect is still due to Cu-rich precipitates at low doses, but the role of manganese-related features becomes pre-dominant at higher doses.