BADERC-Jack L. Strominger

Jack L. Strominger, M.D

Molecular Basis of Immune Recognition

The study of histocompatibility in man and in other vertebrates led to the understanding of the mechanisms of immune recognition and to the discovery of novel molecules and cells involved in these processes, including class I and class II proteins encoded in the major histocompatibility complex of all vertebrates examined and T cell receptors. The normal human response to bacterial and viral infection involves these molecules and results in either the generation of T helper cells and antibodies or of cytotoxic T-lymphocytes. In addition, many important human autoimmune diseases are linked to particular alleles of the class I and class II proteins. Recently, the importance of still another immune recognition system mediated by Natural Killer (NK) cells has become apparent.

My laboratory is focused now on 3 main projects:

1. The role of MHC proteins and of products of other disease susceptibility genes in human autoimmunity, including multiple sclerosis, diabetes, pemphigus vulgaris and ankylosing spondylitis;

2. Activating and inhibitory immunological synapses in human natural killer cells: how they are formed and how they function, particularly in relation to lipid rafts;

3. Uterine decidual lymphocytes and their roles in the immunobiology of pregnancy. This project involves characterizing uterine natural killer (NK) cells, invariant natural killer T (iNKT) cells and T cells and the roles of these lymphocytes and the many unusual proteins they produce in implantation and maintenance of pregnancy.

References:

Strominger JL. Animal antimicrobial peptides: ancient players in innate immunity. J Immunol. 2009 Jun 1;182(11):6633-4.
Li C, Houser BL, Nicotra ML, Strominger JL. HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells. Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5767-72.
Zhang H, Stern JN, Strominger JL. T cell receptors in an IL-10-secreting amino acid copolymer-specific regulatory T cell line that mediates bystander immunosuppression. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3336-41.
Kopcow HD, Rosetti F, Leung Y, Allan DS, Kutok JL, Strominger JL. T cell apoptosis at the maternal-fetal interface in early human pregnancy, involvement of galectin-1. Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18472-7
Kato Z, Stern JN, Nakamura HK, Kuwata K, Kondo N, Strominger JL. Positioning of autoimmune TCR-Ob.2F3 and TCR-Ob.3D1 on the MBP85-99/HLA-DR2 complex. Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15523-8.
Pallandre JR, Krzewski K, Bedel R, Ryffel B, Caignard A, Rohrlich PS, Pivot X, Tiberghien P, Zitvogel L, Strominger JL, Borg C. Dendritic cell and natural killer cell cross-talk: a pivotal role of CX3CL1 in NK cytoskeleton organization and activation. Blood. 2008 Dec 1;112(12):4420-4.
Krzewski K, Strominger JL. The killer's kiss: the many functions of NK cell immunological synapses. Curr Opin Cell Biol. 2008 Oct;20(5):597-605.
Yu MC, Su LL, Zou L, Liu Y, Wu N, Kong L, Zhuang ZH, Sun L, Liu HP, Hu JH, Li D, Strominger JL, Zang JW, Pei G, Ge BX. An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells. Nat Immunol. 2008 Aug;9(8):898-907.
Yang XH, Richardson AL, Torres-Arzayus MI, Zhou P, Sharma C, Kazarov AR, Andzelm MM, Strominger JL, Brown M, Hemler ME. CD151 accelerates breast cancer by regulating alpha 6 integrin function, signaling, and molecular organization. Cancer Res. 2008 May 1;68(9):3204-13.
Stern JN, Keskin DB, Zhang H, Lv H, Kato Z, Strominger JL. Amino acid copolymer-specific IL-10-secreting regulatory T cells that ameliorate autoimmune diseases in mice. Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5172-6.






			Jack L. Strominger, M.D Molecular Basis of Immune Recognition The study of histocompatibility in man and in other vertebrates led to the understanding of the mechanisms of immune recognition and to the discovery of novel molecules and cells involved in these processes, including class I and class II proteins encoded in the major histocompatibility complex of all vertebrates examined and T cell receptors. The normal human response to bacterial and viral infection involves these molecules and results in either the generation of T helper cells and antibodies or of cytotoxic T-lymphocytes. In addition, many important human autoimmune diseases are linked to particular alleles of the class I and class II proteins. Recently, the importance of still another immune recognition system mediated by Natural Killer (NK) cells has become apparent. My laboratory is focused now on 3 main projects: 1. The role of MHC proteins and of products of other disease susceptibility genes in human autoimmunity, including multiple sclerosis, diabetes, pemphigus vulgaris and ankylosing spondylitis; 2. Activating and inhibitory immunological synapses in human natural killer cells: how they are formed and how they function, particularly in relation to lipid rafts; 3. Uterine decidual lymphocytes and their roles in the immunobiology of pregnancy. This project involves characterizing uterine natural killer (NK) cells, invariant natural killer T (iNKT) cells and T cells and the roles of these lymphocytes and the many unusual proteins they produce in implantation and maintenance of pregnancy. References: Strominger JL. Animal antimicrobial peptides: ancient players in innate immunity. J Immunol. 2009 Jun 1;182(11):6633-4. Li C, Houser BL, Nicotra ML, Strominger JL. HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells. Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5767-72. Zhang H, Stern JN, Strominger JL. T cell receptors in an IL-10-secreting amino acid copolymer-specific regulatory T cell line that mediates bystander immunosuppression. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3336-41. Kopcow HD, Rosetti F, Leung Y, Allan DS, Kutok JL, Strominger JL. T cell apoptosis at the maternal-fetal interface in early human pregnancy, involvement of galectin-1. Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18472-7 Kato Z, Stern JN, Nakamura HK, Kuwata K, Kondo N, Strominger JL. Positioning of autoimmune TCR-Ob.2F3 and TCR-Ob.3D1 on the MBP85-99/HLA-DR2 complex. Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15523-8. Pallandre JR, Krzewski K, Bedel R, Ryffel B, Caignard A, Rohrlich PS, Pivot X, Tiberghien P, Zitvogel L, Strominger JL, Borg C. Dendritic cell and natural killer cell cross-talk: a pivotal role of CX3CL1 in NK cytoskeleton organization and activation. Blood. 2008 Dec 1;112(12):4420-4. Krzewski K, Strominger JL. The killer's kiss: the many functions of NK cell immunological synapses. Curr Opin Cell Biol. 2008 Oct;20(5):597-605. Yu MC, Su LL, Zou L, Liu Y, Wu N, Kong L, Zhuang ZH, Sun L, Liu HP, Hu JH, Li D, Strominger JL, Zang JW, Pei G, Ge BX. An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells. Nat Immunol. 2008 Aug;9(8):898-907. Yang XH, Richardson AL, Torres-Arzayus MI, Zhou P, Sharma C, Kazarov AR, Andzelm MM, Strominger JL, Brown M, Hemler ME. CD151 accelerates breast cancer by regulating alpha 6 integrin function, signaling, and molecular organization. Cancer Res. 2008 May 1;68(9):3204-13. Stern JN, Keskin DB, Zhang H, Lv H, Kato Z, Strominger JL. Amino acid copolymer-specific IL-10-secreting regulatory T cells that ameliorate autoimmune diseases in mice. Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5172-6.