Shin, Sunny

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Now showing 1 - 3 of 3
  • Publication
    The D0 Domain of KIR3D Acts as a Major Histocompatibility Complex Class I Binding Enhancer
    (2002-10-07) Khakoo, Salim I; Geller, Ron; Shin, Sunny; Jenkins, Jomaquai A; Parham, Peter
    In contrast to the KIR2D:HLA-C interaction, little is known of KIR3DL1's interaction with HLA-B or the role of D0, the domain not present in KIR2D. Differences in the strength and specificity for major histocompatibility complex class I of KIR3DL1 and its common chimpanzee homologue Pt-KIR3DL1/2 were exploited to address these questions. Domain-swap, deletion, and site-directed mutants of KIR3DL1 were analyzed for HLA-B binding using a novel, positively signaling cell–cell binding assay. Natural ‘deletion’ of residues 50 and 51 from its D0 domain causes Pt-KIR3DL1/2 to bind Bw4+ HLA-B allotypes more avidly than does KIR3DL1. Deletion of these residues from KIR3DL1, or their substitution for alanine, enhanced binding of Bw4+ HLA-B. None of 15 different point mutations in D0 abrogated KIR3DL1 binding to Bw4+ HLA-B. In contrast point mutations in the D1 and D2 domains of KIR3DL1, made from knowledge of KIR2D:HLA-C interactions, disrupted binding to Bw4+ HLA-B. The results are consistent with a model in which D1 and D2 make the principal contacts between KIR3DL1 and HLA-B while D0 acts through a different mechanism to enhance the interaction. This modulatory role for D0 is compatible with natural loss of expression of the D0 domain, a repeated event in the evolution of functional KIR genes.
  • Publication
    An Autonomous CDR3δ is Sufficient for γδ T Cell Recognition of the Nonclassical MHC-I T10/T22
    (2008-07-01) Adams, Erin J; Strop, Pavel; Shin, Sunny; Chien, Yueh-Hsiu; Garcia, K. Christopher
    It remains unclear whether γδ T cell receptors (TCRs) detect antigens in a manner similar to antibodies or αβ TCRs. Here we show that reactivity between G8 and KN6 γδ TCRs and the MHC class Ib molecule T22 can be transplanted, with retention of wild-type ligand affinity, after en bloc grafting of G8 and KN6 CDR3δ loops in place onto the CDR3α loop of an αβ TCR. We also find that a shared sequence motif within CDR3δ loops of all T22-reactive γδ TCRs binds T22 in energetically distinct fashions, and that T10d, which binds G8 with weak affinity, is converted into a high-affinity ligand by a single point mutation. These results demonstrate an unprecedented autonomy of a single CDR3 loop in antigen recognition.
  • Publication
    Thymic Selection Determines γδ T Cell Effector Fate: Antigen-Naive Cells Make Interleukin-17 and Antigen-Experienced Cells Make Interferon γ
    (2008-07-01) Jensen, Kirk D. C; Su, Xiaoqin; Shin, Sunny; Li, Luke; Youssef, Sawsan; Yamasaki, Sho; Steinman, Lawrence; Saito, Takashi; Locksley, Richard M; Davis, Mark M; Baumgarth, Nicole; Chien, Yueh-hsiu
    γδ T cells contribute uniquely to host immune competence, but how they do so remain unclear. Here, by analyzing T10/T22-specific γδ T cells in mice with different T10/T22 expression patterns, we find that encountering antigen in the thymus is neither required nor inhibitory for the development of these cells. Instead, ligand recognition determines which of two distinct functional subsets γδ T cells will become. When triggered through the TCR, lymphoid-γδ T cells that encounter ligand during development produce IFNγ, while those that develop in the absence of ligand make IL-17, a major inducer of granulopoiesis during inflammation. Indeed, we find large fractions of IL-17+ γδ T cells from the draining lymph nodes immediately after peptide/CFA immunization and days before the appearance of antigen specific IL-17+ αβ T cells. This suggests a critical role for γδ T cells as ‘initial providers’ of IL-17 in an inflammatory response to novel antigens.