Analysis of junctional diversity in the preferential V delta 1-J delta 1 rearrangement of fresh T-acute lymphoblastic leukemia cells by in vitro gene amplification and direct sequencing.
To define the junctional diversity of T-cell antigen receptor delta gene rearrangements in fresh T-acute lymphoblastic cells and to correlate cell phenotype with the coding potential of rearrangements, we determined the junctional nucleotide sequences of 13 T-cell antigen receptor delta gene rearrangements involving the preferentially rearranged V (V delta 1) and J (J delta 1) segments using in vitro gene amplification and direct sequencing. We showed that, as in gamma delta+ cell lines, extensive junctional diversity exists in these clones and that this diversity is due both to random nucleotide deletions/additions and to the use of at least two D delta segments. We also showed that a high percentage of these rearrangements are potentially translatable (7:13) and that such functional rearrangements occur in both surface CD3+ and CD3- cells. Comparison of alpha beta versus gamma delta surface expression demonstrates that all CD3+ T acute lymphoblastic leukemias with a functional V delta 1-J delta 1 rearrangement express a surface gamma delta receptor and are recognized by the anti-delta monoclonal antibody delta TCS1, whereas a control CD3+ gamma delta+ leukemic case that had not undergone V delta 1 rearrangement was delta TCS1-. In addition, expression of this monoclonal antibody is not restricted by V gamma or C gamma usage or by the covalent or noncovalent link between gamma and delta chains.
Macintyre
E
E
Laboratoire d'Hématologie Moleculaire, Hôpital Saint Louis, Paris, France.
d'Auriol
L
L
Amesland
F
F
Loiseau
P
P
Chen
Z
Z
Boumsell
L
L
Galibert
F
F
Sigaux
F
F
D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D005784:Gene Amplification; D015329:Gene Rearrangement, T-Lymphocyte; D005796:Genes; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta
D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta