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T lymphocytes recognize and destroy invading pathogens through an assembly of proteins called the T cell antigen receptor (TCR) complex. The TCR has protein subunits that are highly variable and responsible for target recognition (either α/β or γ/δ) and subunits that are invariant proteins and serve to transmit signals (CD3γδε and ζ). This critical protein assembly (the TCR) controls not only the behavior of mature T lymphocytes but also their development in the thymus. My laboratory seeks to understand how T cell development is controlled by the TCR and how these developmental process are corrupted during development of cancer. There are two types of TCR variable proteins, α/β and γ/δ. Utilization of these α/β and γ/δ pairs characterizes two distinct types of T lineages, α/β and γ/δ, respectively. These two T lineages are thought to arise from a single immature precursor in the thymus. We are attempting to identify the cellular factors that are essential for transmitting the signals that direct adoption of these alternate fates (i.e., αβ or γδ). We hypothesize that the genes, which are essential for normal cell development, are also likely to regulate development of cancer. Indeed, we have recently identified such a gene, which encodes a component of the cellular machine responsible for synthesis of all cellular proteins, the ribosome. This component, termed Rpl22, is not only essential for normal T cell development, but also may contribute to development of human T cell cancers termed T acute lymphoblastic leukemia (T-ALL).

1. Lauritsen JPH, Wong GW, Lee SY, Lefebvre JM, Ciofani M, Rhodes M, Kappes DJ, Zúñiga-Pflücker JC, Wiest DL. Marked induction of the helix-loop-helix protein Id3 promotes the γδ T cell fate and renders their functional maturation Notch-independent. Immunity. 2009;31:565-75. PubMed
2. Anderson SJ, Lauritsen JPH, Hartman M, DiGeorge-Foushee AM, Gerhardt B, Lefebvre JM, Oravecz T, Wiest DL. Defect in ribosomal protein L22 selectively impairs αβ T cell development by activation of a p53-dependent checkpoint. Immunity. 2007;26:759-772. PubMed
3. Ciofani M, Knowles GC, Wiest DL, von Boehmer H, Zúñiga-Pflücker JC. Stage-specific and differential dependency at the αβ/&gamma&delta T lineage bifurcation branchpoint. Immunity. 2006;25:105-16. PubMed
4. Yamasaki S, Ishikawa E, Sakuma M, Ogata K, Sakata-Sogawa K, Hiroshima M, Wiest DL., Tokunaga M, Saito T. Mechanistic basis of pre-T cell receptor-mediated autonomous signaling critical for thymocyte development. Nature Immunology. 2006;7:67-75. PubMed
5. Haks MC, Lefebvre JM, Lauritsen JPH, Carleton MO, Rhodes M, Kappes DJ, Wiest, DL. Attenuation of γδTCR signaling efficiently diverts thymocytes to the αβ lineage. Immunity. 2005;22:595-606. PubMed