ABSTRACT
It is becoming increasingly clear that T cell responses against many antigens are dominated by public α/ß T cell receptors (TCRs) with restricted heterogeneity. Because expression of public TCRs may be related to resistance, or predisposition to diseases, it is relevant to measure their frequencies. Although staining with tetrameric peptide/major histocompatibility complex (pMHC) molecules gives information about specificity, it does not give information about the TCR composition of the individual T cells that stain. Moreover, next-generation sequencing of TCR does not yield information on pairing of α- and ß-chains in single T cells. In an effort to overcome these limitations, we have here investigated the possibility of raising a monoclonal antibody (moAb) that recognizes a public TCR. As a model system, we have used T cells responding to the 91-101 CDR3 peptide of an Ig L-chain (λ2³¹5), presented by the MHC class II molecule I-E(d). The CD4⺠T cell responses against this pMHC are dominated by a receptor composed of Vα3Jα1;Vß6DßJß1.1. Even the V(D)J junctions are to a large extent shared between T cell clones derived from different BALB/c mice. We here describe a murine moAb (AB10) of B10.D2 origin that recognizes this public TCR, while binding to peripheral T cells is negligible. Binding of the moAb is abrogated by introduction of two Gly residues in the D-J junction of the CDR3 of the ß-chain. A model for the public TCR determinant is presented.
