Idiotypic analysis of anti-I-Ak monoclonal antibodies. II. Detection of shared idiotopes on syngeneic BALB/c and allogeneic A.TH-derived anti-I-Ak mAb by BALB/c-derived anti-I-Ak anti-idiotypic mAb
Devaux, C.A.; Phillips, M.L.; Delovitch, T.L.
Journal of Immunology 133(5): 2595-2602
The IA2, IIID1, and VC6 BALB/c-derived anti-11-5 anti-idiotypic (anti-Id) monoclonal antibodies (mAb) described in the companion paper were used to study the idiotopes expressed by a panel of 13 anti-I-Ak and 10 anti-I-Ek mAb. IA2 and IIID1, which detect binding-site-related idiotopes of the syngeneic BALB/c-derived 11-5 mAb, each react with public idiotope(s) (IdX) of two allogeneic A.TH-derived anti-I-Ak mAb (8B and 39J). VC6, which detects an 11-5 idiotope that differs from the IA2 and IIID1 idiotopes, binds to the 8B but not the 39J mAb. The three anti-Id mAb examined do not bind to idiotopes on 11 other anti-I-Ak or to 10 other anti-I-Ek mAb tested. These data demonstrate that mice immunized with a murine anti-I-Ak mAb probably produce syngeneic anti-IdX serum antibodies. Furthermore, they suggest that the 11-5 IdX markers identified are shared by alloantibodies of the BALB/c (Igh1a) and A.TH (Igh1e) mouse strains and may be expressed independently of Igh-C allotype markers. The sharing of idiotopes between the 11-5, 8B (anti-Ia.2), and 39J (anti-Ia.19) mAb led us to reinvestigate the antigenic specificity of the 11-5 mAb and the genetic complexity of the serologically detectable Ia.2 and Ia.19 epitopes present on I-Ak molecules. Two main points emerge from these studies. First, the 11-5 BALB/c-derived anti-I-Ak mAb, previously considered to have an anti-Ia.2 specificity, was shown by direct binding and competition binding assays to possess instead a reactivity pattern more compatible with that of an anti-Ia.19 mAb. Second, the anti-Ia.2 and anti-Ia.19 mAb, which were provisionally considered to bind epitopes in a single region of an I-Ak molecule, termed epitope cluster IV, actually define at least four different subgroups of this cluster. These subgroups are designated as IV A-D, and IV D is detected by the 11-5 and 39J anti-Ia.19 mAb. This tentative subdivision of I-Ak epitope cluster IV suggests there exists a minimum of seven topologically distinguishable regions of an I-Ak molecule that give rise to polymorphic allodeterminants, some or all of which may mediate lymphocyte interaction.