The present invention includes compositions and methods that include antibodies that selectively neutralize a bioactivity of at least two interferon alpha ("IFNa") protein subtypes for the protein subtypes A, 2, B2, C, F, G, H2, 1, J1, K, 4a, 4b and WA, but does not neutralize at least one bioactivity of IFNa protein subtype D. Examples of bioactivity for measurement include activation of the MxA promoter or antiviral activity and variants, derivatives and fragments thereof. The invention also includes host cells, hybridomas and plasmacytomas that produce antibodies. Because of their unique selectivity and affinity, the antibodies of the present invention are useful to detect IFNa subtypes in sample or tissue and/or for therapeutic applications that include, but are not limited to the treatment and/or amelioration of an IFNa related disorder such as SLE, lupus, type 1 diabetes, psoriasis, AIDS and Graft versus Host Disease.