Allotype-linked genetic control of a polymorphic V_H framework determinant on mouse T-helper cell receptors

Abstract

The immune system confronts antigens through the variable domains of antigen receptors on lymphocytes. The biochemistry of these antigen receptors is fundamental to the understanding of the immune system. Whilst B cells use immunoglobulins (Ig) as antigen receptors, T cells use unknown molecules which appear to differ from Ig except for the shared variable region of the Ig heavy chain (V_H). The notion that T-cell receptors consist, at least in part, of immunoglobulin V_H regions stems largely from experiments using anti-idiotypic antibodies^1–3. Much serological and genetic evidence has meanwhile accumulated suggesting that V_H associated idiotypic determinants are shared between Ig molecules and the antigen receptors of certain classes of T cells including helper cells, cells proliferating on mixed lymphocyte reaction delayed type hypersensitive reactive cells, and cytotoxk T cells ^4–7. This pertains to structural elements associated with hypervariable portions of V_H, but data on framework elements of V_H regions of T cells are scarce^8,9. We have previously reported that mouse T-cell receptors react with a rabbit antibody to the V_H fragment of MOPC 315 (anti-V_H)^10–12. The V_H framework determinants appeared polymorphic in that the T-helper cells as well as the immunoglobulin heavy (H) chains of a variety of mouse strains reacted equally well, except in the case of strain AKR^12,13. We report here the genetic control of the V_H framework determinant whose expression through T-helper cells seems to be governed by at least one gene linked to the Igh allotype linkage group. Thus, this V_H framework determinant behaves like the rabbit V_H region allotypes which are expressed on both immunoglobulin H chains and T-cell receptors^8,9. These data suggest the expression of entire V_H regions in T-cell antigen receptors^1–3.