AT cell clone expresses two T cell receptor α genes but uses one αβ heterodimer for allorecognition and self MHC-restricted antigen recognition

M Malissen, J Trucy, F Letourneur, N Rebai, DE Dunn… - Cell, 1988 - cell.com
M Malissen, J Trucy, F Letourneur, N Rebai, DE Dunn, FW Fitch, L Hood, B Malissen
Cell, 1988cell.com
All of the T cell receptor a-and P-chain rearrangements present in a dual reactive T cell
clone were characterized. This clone exhibits allelic exclusion of its P-chain genes in that
only one of the two alleles is productively rearranged. Unexpectedly, it displays two
productive Va-gene rearrangements, which are both transcribed into 1.5 kb mRNA. The
contribution of each of the two productive a genes to the dual recognition was analyzed by
gene transfer. To this end, each of the two a genes was separately transfected with the …
Summary
All of the T cell receptor a-and P-chain rearrangements present in a dual reactive T cell clone were characterized. This clone exhibits allelic exclusion of its P-chain genes in that only one of the two alleles is productively rearranged. Unexpectedly, it displays two productive Va-gene rearrangements, which are both transcribed into 1.5 kb mRNA. The contribution of each of the two productive a genes to the dual recognition was analyzed by gene transfer. To this end, each of the two a genes was separately transfected with the single productively rearranged p gene. Transfer of only one of the two ab combinations restored both allogeneic MHC recognition and self MHC-restricted antigen recognition. Thus, T cell dual recognition results from the cross-reactive recognition of an allo-MHC product by a single antigen-specific and MHC-restricted aB T cell receptor. Furthermore, the presence of two productively rearranged a-chain genes in a T cell clone raises questions concerning the level at which allelic exclusion operates in T cells. introduction
Receptors for antigen on T cells are made up of two chains, a and/3, each with a clonally variable (V) region. During T cell maturation, a-chain V region genes are formed by the assembly of single members from each of two separate sets of germ-line gene segments denoted variable (Va) and joining (Ja). Similarly, P-chain V region genes are assembled from three separate sets of gene segments called variable (VP), diversity (Dp), and joining (Jp). Due to the imprecision of the recombinational process, Va to Ja or VP to Dp-Jp joining events could result either in a productive rearrangement that maintains an open reading frame throughout the V gene or in a nonproductive rearrangement in which the gene segments are recombined out-of-frame (reviewed in Alt et al., 1987). As a corollary, because T lymphocytes are diploid cells, this assembly process could potentially generate in a sin-
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