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 Dz 2 Lz 4 wherein the z 2 is an amino acid residue and z 4 is threonyl or isoleucyl. Exemplary molecules comprise a sequence of the formulae a 1 a 2 a 3 CDa 6 La 8 a 9 a 10 Ca 12 a 13 a 14 (SEQ.ID.NO:100), b 1 b 2 b 3 Cb 5 b 6 Db 8 Lb 10 b 11 b 12 b 13 b 14 Cb 16 b 17 b 18 (SEQ.ID.N0:104), c 1 c 2 c 3 Cc 5 Dc 7 Lc 9 c 10 c 11 c 12 c 13 c 14 Cc 16 c 17 c 18 (SEQ.ID.NO:105), d 1 d 2 d 3 Cd 5 d 6 d 7 WDd 10 Ld 13 d 14 d 15 Cd 16 d 17 d 18 (SEQ.ID.N0:106), e 1 e 2 e 3 Ce 5 e 6 e 7 De 9 Le 11 Ke 13 Ce 15 e 16 e 17 e 19 (SEQ.ID.NO:107), f 1 f 2 f 3 Kf 5 Df 5 Lf 9 f 10 f 12 f 13 f 14 (SEQ.ID.NO:109) wherein the substituents are defined in the specification. The invention further comprises compositions of matter of the formula (X 1 ) a -V 1 -(X 2 ) b wherein V 1 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.
