Antibodies directed against the MHC-I molecule H-2D(d) complexed with an antigenic peptide: Similarities to a T cell receptor with the same specificity

alpha beta TCRs, which use an Ab-like structure to form a combining site, r ecognize molecular complexes consisting of peptides bound to MHC class I(MH C-I) or class II (MHC-II) molecules, To explore the similarities and differ ences between Ab acid T cell recognition of similar structures, we have iso lated two mAbs, KP14 and KP15, that specifically bind H-2D(d) complexed wit h an HIV envelope gp160-derived peptide, P18-I10. These Abs are MHC and pep tide specific, Fine specificity of mAb binding was analyzed using a panel o f synthetic peptides, revealing similarities between the mAb and a cloned T CR with the same specificity. These two mAbs used the same V-H and J(H) gen e segments, but different D, V kappa, and J kappa genes. Administered in vi vo, mAb KP15 blocked the induction of CTL specific for recombinant vaccinia virus-encoded gp160, indicating its ability to bind endogenously generated MHC/peptide complexes. Analysis of the fine specificity of these mAbs in t he context of their encoded amino acid sequences and the known three-dimens ional structure of the H-2D(d)/P18-I10 complex suggests that they bind in a n orientation similar to that of the TCR, Thus, the plasticity of the B cel l receptor repertoire and the structural similarities among BCR and TCR all ow Abs to effectively mimic alpha beta TCRs. Such mAbs may be useful in the therapeutic modulation of immune responses against infectious agents or ha rmful self Ags as well as in tracing steps in Ag processing.