The present invention concerns therapeutic agents that modulate the activity of TALL-1. In accordance with the present invention, modulators of TALL-1 may comprise an amino acid sequence Dz2Lz4 wherein z2 is an amino acid residue and z4 is threonyl or isoleucyl. Exemplary molecules comprise a sequence of the formulae(SEQ ID NO: 100)a1a2a3CDa6La8a9a10Ca12a13a14,(SEQ ID NO: 104)b1b2b3Cb5b6Db8Lb10b11b12b13b14Cb16b17b18(SEQ ID NO: 105)c1c2c3Cc5DC7Lc9c10c11c12c13c14Cc16c17c18(SEQ ID NO: 106)d1d2d3Cd5d6d7WDd10Ld13d14d15Ld16d17d18(SEQ ID NO: 107)e1e2e3Ce5e6e7De9Le11Ke13Ce15e16e17e18(SEQ ID NO: 109)f1f2f3Kf5Df7Lf9f10Qf12f13f14wherein the substituents are as defined in the specification. The invention further comprises compositions of matter of the formula(X1)a-V1-(X2)b wherein V1 is a vehicle that is covalently attached to one or more of the above TALL-1 modulating compositions of matter. The vehicle and the TALL-1 modulating composition of matter may be linked through the N- or C-terminus of the TALL-1 modulating portion. The preferred vehicle is an Fc domain, and the preferred Fc domain is an IgG Fc domain.
