Change in antigen specificity of cytotoxic T lymphocytes is associated with the rearrangement and expression of a T-cell receptor beta-chain gene.

Epplen, Jörg T.; Bartels, Frauke; Becker, Andrea C.; Nerz, Gabi; Prester, Marlot; Rinaldy, Augustinus; Simon, Markus M.

doi:10.1073/pnas.83.12.4441

Cited by 15 publications

(2 citation statements)

References 33 publications

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“…For TCR-VDJ recombination assay, we used the mixture of different Vh family primers (35) along with Jb2-39 59-TGAGAGCTGTCTCCTACTATCGATT-39 and for TCR-DJ recombination assay, Db1-59 59-CAGCCCCTTCAGCAAAGAT-39 and Jb1-39 59-CCTAAGTTCCTTTCCAAGACCAT-39. From the cDNA synthesized from the sorted cells, the transcribed TCRb genes were analyzed using mixtures of different Vh family primers (35) along with a constant gene primer (36).…”

Section: Tcrb Recombination Analysismentioning

confidence: 99%

ARID1a Associates with Lymphoid-Restricted Transcription Factors and Has an Essential Role in T Cell Development

Astori

Tingvall-Gustafsson

Kuruvilla

et al. 2020

The Journal of Immunology

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Maturation of lymphoid cells is controlled by the action of stage and lineage-restricted transcription factors working in concert with the general transcription and chromatin remodeling machinery to regulate gene expression. To better understand this functional interplay, we used Biotin Identification in human embryonic kidney cells to identify proximity interaction partners for GATA3, TCF7 (TCF1), SPI1, HLF, IKZF1, PAX5, ID1, and ID2. The proximity interaction partners shared among the lineagerestricted transcription factors included ARID1a, a BRG1-associated factor complex component. CUT&RUN analysis revealed that ARID1a shared binding with TCF7 and GATA3 at a substantial number of putative regulatory elements in mouse T cell progenitors. In support of an important function for ARID1a in lymphocyte development, deletion of Arid1a in early lymphoid progenitors in mice resulted in a pronounced developmental arrest in early T cell development with a reduction of CD4 + CD8 + cells and a 20-fold reduction in thymic cellularity. Exploring gene expression patterns in DN3 cells from Wt and Arid1a-deficient mice suggested that the developmental block resided in the DN3a to DN3b transition, indicating a deficiency in b-selection. Our work highlights the critical importance of functional interactions between stage and lineage-restricted factors and the basic transcription machinery during lymphocyte differentiation.

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Section: Tcrb Recombination Analysismentioning

confidence: 99%

ARID1a Associates with Lymphoid-Restricted Transcription Factors and Has an Essential Role in T Cell Development

Astori

Tingvall-Gustafsson

Kuruvilla

et al. 2020

The Journal of Immunology

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“…The elevated y chain and decreased a chain expression in later stages Using an oligonucleotide hybridization probe specific for this V region it can be seen that VAK expression is absent in CTLL.l but present in all variants (Fig. 4E) including CTLL.2 (not shown) which seems to consist of a mixture of CTLL.l and CTLL.3 [36]. Interestingly, the VAK V region expressed in the variant CTLL is highly homologous to the human fl chain V region YT35 which is expressed in at least two human T cell leukemia lines, MOLT 3 and Jurkat [37].…”

Section: Expression Of T Cell Receptor Chain Genes In H-y-specificmentioning

confidence: 92%

Leukemic cells arise from cloned cytotoxic lymphocytes during cell culture

et al. 1986

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In spite of many promising attempts to apply T cell clones to questions of in vitro and in vivo function of T cells it is still unclear to what extent continuous propagation of T lymphocytes in vitro effects their original properties. This study describes the appearance of malignant cells from long-term cultured C57BL/6 (B6) cytotoxic T lymphocytes (CTL). Four out of five T cell lines (CTLL.1,3,4,5) representing distinct stages of development of T effector cells in vitro were repeatedly cloned and all five CTLL were tested for various cellular parameters. It is shown that transformation of H-Y-specific CTLL into malignant cells in vitro was accompanied by alterations in growth characteristics, successive loss of specificity and cytolytic function and by quantitative changes in the expression of cell surface markers. Whereas growth of the H-Y-specific CTLL (CTLL.1) was dependent on antigen and concanavalin A (Con A) supernatant (Con ASN) the CTLL variants could be either maintained in Con ASN alone (CTLL.3) or in the absence of both antigen and lymphokine sources (CTLL.4,5). CTLL.1 was cytolytic for male B6 target cells and lysed P815 tumor targets in the presence but not the absence of lectin. In contrast, CTLL.3 lost its original specificity but lysed P815 cells in the absence or presence of lectin. CTLL.2 representing an intermediary stage showed cytolytic activity on both male B6 and P815 target cells. In contrast, CTLL.4 and CTLL.5 lost the ability to lyse any of the indicated target cells. Although all CTLL expressed the surface markers Thy-1, Lyt-2, Kb, Db and interleukin 2 receptor (IL 2 R), Thy-1 and Lyt-2 markers were drastically reduced and Kb/Db and IL 2 R structures significantly increased on CTLL.4 and CTLL.5 compared to CTLL.1,2,3. In addition, multiple karyotypic alterations including the appearance of metacentric chromosomes were observed in long-term cultured CTLL. Investigations on the expression of the alpha-, beta-, and gamma-chains of the T cell antigen receptor in CTLL.1-5 indicate that all three chains were expressed as mRNA irrespective of whether the lymphocytes expressed their original specificity and/or function. However, distinct beta variable chain genes were used by H-Y-specific CTLL and its long-term culture variants CTLL.2 and CTLL.3 suggesting that the expression of the new specificity was accompanied by the rearrangement of a new beta-chain gene in T effector cells.(ABSTRACT TRUNCATED AT 400 WORDS)

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Growth‐dependent variation of major histocompatibility complex (MHC) restriction and expression of Ly‐2 and CD3/α/βT cell receptor in cloned cytotoxic T cells

et al. 1988

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The specificity of major histocompatibility complex (MHC)-restricted antigen recognition by cytotoxic T cells (CTL) has been clearly correlated to the alpha/beta T cell receptor (TcR) complex on the T cell surface. Occasional changes in the specificity of in vitro cultivated CTL clones, therefore, have been suspected to result from alterations of the genes coding for the TcR alpha and/or beta chain. Here we demonstrate that pronounced variations in the stringency of MHC restriction, previously reported to occur during long-term culture of 2,4,6-trinitrophenyl (TNP)-specific CTL clones, may occur rapidly in a growth-dependent, reversible manner, i.e. without structural TcR variation. Several H-2b TNP-specific CTL clones were shown to possess strong cross-reactivity for H-2k TNP target cells when seeded at low cell numbers, but exhibit reduced or undetectable cross-reaction to H-2k TNP in high-density cultures. Another clone revealed "heteroclitic" properties with significantly stronger cytotoxic activity towards allogeneic (H-2k) than syngeneic (H-2b) TNP-modified target cells. In this case dilute cultures appeared as exclusively allo-MHC restricted, whereas dense cultures were allo/self cross-restricted. In all instances these phenomena were accompanied by cell density-dependent quantitative changes in the expression of Ly-2 and T cell antigen receptor. CTL from dilute cultures had at least 2-fold higher surface concentrations of Ly-2 and CD3 antigens than cells from dense cultures while other surface markers such as Thy-1 or LFA-1 were completely identical. No such effects were observed for CTL clones exhibiting cell density-independent specificity patterns. We conclude from these findings that (a) the stringency of MHC restriction specificity may be significantly affected by the amount of expressed TcR and/or Ly-2 molecules, (b) CTL possess mechanisms to regulate Ly-2 and TcR expression and, hence, their MHC-restricted antigen recognition, and (c) the ability to regulate Ly-2 and TcR expression may be altered during prolonged culture of a CTL clone.

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Change in antigen specificity of cytotoxic T lymphocytes is associated with the rearrangement and expression of a T-cell receptor beta-chain gene.

Cited by 15 publications

References 33 publications

ARID1a Associates with Lymphoid-Restricted Transcription Factors and Has an Essential Role in T Cell Development

ARID1a Associates with Lymphoid-Restricted Transcription Factors and Has an Essential Role in T Cell Development

Leukemic cells arise from cloned cytotoxic lymphocytes during cell culture

Growth‐dependent variation of major histocompatibility complex (MHC) restriction and expression of Ly‐2 and CD3/α/βT cell receptor in cloned cytotoxic T cells

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