Cross-Reactions of Anti-Immunoglobulin Sera with Synthetic T-Cell Receptor β Peptides: Mapping on a 3-Dimension Model

Abstract

The derived amino acid sequences of human T-cell receptor β chain shows significant homology to λ light chains of immunoglobulins in its variable, joining, and constant regions. We assessed the cross-reactivity between Tcr β chains and immunoglobulin light chains by determining the capacity of rabbit antisera to human or murine immunoglobulins to react to a synthesized set of nested, overlapping 16-mer peptides corresponding to the VDJC sequence of the Tcr β chain YT35. The observed reactivities were consistent with homologies to λ and k light chains, the strongest reactivity being with a peptide that corresponds to the “switch peptide” of light chains, as assessed by ELISA binding and competitive inhibitions assays. Other regions reactive with anti-light chain sera corresponded to CDR1 and Fr3 segments of the variable domain and a segment of the constant region predicted to loop out of the tight globular structure. The peptide immunochemical results, together with the identification of specific regions of sequence correspondence between Tcr β and the characterized λ light chain Mcg, allowed us to develop a 3-dimensional model of the β chain consistent with its role in antigen recognition.