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Specificity mapping of human anti‐T cell receptor monoclonal natural antibodies: defining the properties of epitope recognition promiscuity
Author(s) -
Robey Ian F.,
Edmundson Allen B.,
Schluter Samuel F.,
Yocum David E.,
Marchalonis John J.
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0884com
Subject(s) - epitope , monoclonal antibody , linear epitope , antibody , t cell receptor , complementarity determining region , biology , epitope mapping , antigen , microbiology and biotechnology , chemistry , computational biology , t cell , genetics , immune system
The classical concept of antibody binding is defined as an exclusive and high‐affinity interaction with one epitope. The emerging reality about antibody combing sites, however, is that some can bind unrelated determinants. The studies presented here define this quality as epitope recognition promiscuity by analyzing the capacity of monoclonal human auto‐antibodies to bind sets of overlapping peptides duplicating the complete structures of T cell receptor (TCR) α and β chains and immunoglobulin λ chain. We assessed the binding of these monoclonal antibodies (mAbs) to a set of homologous peptides corresponding to the CDR1 segments of human Vβ gene products, a major epitope used in the selection of the antibodies. We present data on the binding characteristics of four human mAbs selected for the ability to bind TCR epitopes. These mAbs are IgM molecules with V H and V L sequences in germline configuration, but have diverse V H CDR3 regions. These studies aim to characterize the property of epitope promiscuity and show that the relationship between the binding site and its epitope is a complex interaction and unpredictable from antigen sequence alone. Our results support the conclusion that epitope recognition promiscuity is a genuine feature of antibody and TCR recognition.