B7 and 34B7 Monoclonal Antibodies: A Theoretical Approach to the Molecular Basis of Immunoglobulin Cross-Reactive Antibodies

Neonatal natural antibodies (NAbs) are characterized by their high degree of idiotypic cross reactivity, together with some restrictions in the genetic mechanisms of variable region diversity. We report here the immunogenetic analysis of two anti-idiotype antibodies (B7 and 34B7 monoclonal antibodies [MAbs]), which are also polyreactive as NAbs. Evidence of a process of somatic mutations were found for heavy and light chain variable regions of both antibodies. A phylogenetic analysis of the V_HJ558 family showed that the immunoglobulin cross-reactivity displayed by B7 and 34B7 MAbs is not restricted to a particular subgroup of this family. Moreover, we identified amino acid motifs in the CDR H1 and H2 of B7 and 34B7 MAbs that are also present in high proportion in immunoglobulin cross-reactive antibodies (ICRA) reported in the Kabat database. We propose that these regions are involved in ICRA activity.