Antibodies directed against the MHC-I molecule H-2Dd complexed with an antigenic peptide: similarities to a T cell receptor with the same specificity.
alphabeta TCRs, which use an Ab-like structure to form a combining site, recognize molecular complexes consisting of peptides bound to MHC class I (MHC-I) or class II (MHC-II) molecules. To explore the similarities and differences between Ab and T cell recognition of similar structures, we have isolated two mAbs, KP14 and KP15, that specifically bind H-2D(d) complexed with an HIV envelope gp160-derived peptide, P18-I10. These Abs are MHC and peptide specific. Fine specificity of mAb binding was analyzed using a panel of synthetic peptides, revealing similarities between the mAb and a cloned TCR with the same specificity. These two mAbs used the same V(H) and J(H) gene segments, but different D, Vkappa, and Jkappa genes. Administered in vivo, 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 the context of their encoded amino acid sequences and the known three-dimensional structure of the H-2D(d)/P18-I10 complex suggests that they bind in an orientation similar to that of the TCR. Thus, the plasticity of the B cell receptor repertoire and the structural similarities among BCR and TCR allow Abs to effectively mimic alphabeta TCRs. Such mAbs may be useful in the therapeutic modulation of immune responses against infectious agents or harmful self Ags as well as in tracing steps in Ag processing.
Polakova
K
K
Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases and Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Plaksin
D
D
Chung
D H
DH
Belyakov
I M
IM
Berzofsky
J A
JA
Margulies
D H
DH
D000595:Amino Acid Sequence; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D000918:Antibody Specificity; D001483:Base Sequence; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D006183:H-2 Antigens / Q000276:immunology* / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology* / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D007166:Immunosuppressive Agents; C416862:KP14 monoclonal antibody; C416863:KP15 monoclonal antibody; D009842:Oligopeptides; D016693:Receptors, Antigen, T-Cell, alpha-beta