The process of self-education selects appropriate antigen-specific T cell receptors (TCRs) which are tolerant to determinants of the major histocompatibility locus (MHC) alone, but which can interact with self-MHC in the presence of antigen. Recently the TCR has been characterized at the molecular level. The TCR is constituted by the association of at least two polypeptide chains, alpha and beta, which contribute to the specificity of the T cell. These two polypeptides are encoded by two distinct sets of genes. In addition to these two subunits, a third set of genes encoding a putative TCR molecule, called gamma chain, has been found expressed at the mRNA level in certain populations of T cells. Nevertheless, the protein product of this gene as well as its function are not known to date. The genes encoding these three polypeptides are present in an unrearranged form in germline DNA and undergo specific rearrangement in DNA of cells of the T cell lineage. The pattern of these rearrangements presumably controls the specificity and tolerance of the T cells. We have described a situation in humans following MHC haploidentical Bone Marrow Transplantation (BMT) in which tolerance to donor MHC determinants did not occur, leading to the circulation of donor T cells displaying reactivity towards donor histocompatibility determinants. An autoreactive T cell line from this patient has been grown in vitro. We propose to study the expression of the TCR genes in this autoreactive cell line. The same study will also be done in mice in which it has been possible to induce severe auto-Graft-versus-Host (GVH) reactions in vivo after syngeneic BMT. The study of TCR expression in these two abnormal situations should give us some insight into the process of normal self-education at the molecular level, and should contribute to transplantation therapy in general.
