Identification of amino acid residues implicated in the cross-reaction between immunoglobulin VH and a T cell receptor molecule.

The problem of the relationship between the immunoglobulin-related T cell receptor (IgT) and classical immunoglobulin heavy chain variable regions (VH) was approached by determining the capacity of a xenoantiserum made against the immune affinity purified product of a permanent in vitro T cell line of mature, amplifier phenotype to react with human and murine monoclonal immunoglobulins with completely sequenced VH regions. Most of the amino acid residues identified as critical for the observed serological cross-reaction were localized within the disulfide-bonded loop and all of these occur on the surface of the 3-dimensional structure of the VH molecule. The most strongly correlated residues were restricted to the second complementarity determining region and the third framework region. This suggests that IgT need not contain complete VH regions, but that the serological cross-reaction might result from the insertion of 'minigenes' into a non-immunoglobulin framework or from short stretches of shared sequence between VH and the products of separate VT gene cluster.