Spontaneous T cell antigen receptor variants of a human T leukemia cell line.
We have sought to address the question of clonal variation of TCR within a human T leukemia cell line, HPB-ALL. To do so, a panel of anti-idiotypic antibodies was produced and the cell line examined for variants. We isolated both spontaneous idiotype and receptor-negative variants without applying mutagens or any selective pressure other than sorting the cells. These sorted and cloned populations are all clonally related to each other as shown by their beta-TCR locus gene rearrangements. The idiotype variants have alpha-chains which are differentially glycosylated, but they have the same size core protein after treatment with peptide N-glycosidase F to remove their carbohydrate side chains. This probably accounts for their idiotypic difference, since the antibody that distinguishes them appears dependent upon glycosylation for its binding, as shown by immunoprecipitation in the presence versus the absence of tunicamycin, which inhibits glycosylation from occurring. The idiotype variants differed from one another in variable region sequences by only a single amino acid substitution in the beta-chain, which is likely not important for the idiotypic difference. The receptor-negative variant produces both alpha- and beta-mRNA and cytoplasmic protein for TCR, but fails to transport this protein to the cell surface. We conclude that idiotype and receptor-negative variants of a T cell clone can occur in the absence of appreciable somatic mutation.
Maecker
H T
HT
Stanford University Medical School, CA 94305.
Levy
R
R
D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D001666:Binding Sites, Antibody; D002460:Cell Line; D002999:Clone Cells / Q000145:classification / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D014644:Genetic Variation; D006031:Glycosylation; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000032:analysis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000145:classification / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell