Kajal Hamidzadeh

Publications (2)7.24 Total impact

• Article: Critical role of activation induced cytidine deaminase in Experimental Autoimmune Encephalomyelitis.

  Yonglian Sun, Ivan Peng, Kate Senger, Kajal Hamidzadeh, Mike Reichelt, Miriam Baca, Ronald Yeh, Maria N Lorenzo, Andrew Sebrell, Christopher Dela Cruz, [......], Jiansheng Wu, Tao Sai, Merone Roose-Girma, Søren Warming, Mercedesz Balazs, Lino C Gonzalez, Patrick Caplazi, Flavius Martin, Jason Devoss, Ali A Zarrin
  [show abstract] [hide abstract]
  ABSTRACT: Multiple Sclerosis (MS) is a neurodegenerative autoimmune disorder caused by chronic inflammation and demyelination within the central nervous system (CNS). Clinical studies in MS patients have demonstrated efficacy with B cell targeted therapies such as anti-CD20. However, the exact role that B cells play in the disease process is unclear. Activation Induced cytidine deaminase (AID) is an essential enzyme for the processes of antibody affinity maturation and isotype switching. To evaluate the impact of affinity maturation and isotype switching, we have interrogated the effect of AID-deficiency in an animal model of MS. Here, we show that the severity of experimental autoimmune encephalomyelitis (EAE) induced by the extracellular domain of human myelin oligodendrocyte glycoprotein (MOG1-125) is significantly reduced in Aicda deficient mice, which, unlike wild type mice, lack serum IgG to myelin associated antigens. MOG specific T cell responses are comparable between wild type and Aicda knockout mice suggesting an active role for antigen experienced B cells. Thus affinity maturation and/or class switching are critical processes in the pathogenesis of EAE.
  Autoimmunity 11/2012; · 2.47 Impact Factor
• Article: Evolutionarily conserved paired immunoglobulin-like receptor α (PILRα) domain mediates its interaction with diverse sialylated ligands.

  Yonglian Sun, Kate Senger, Tomasz K Baginski, Anita Mazloom, Yvonne Chinn, Homer Pantua, Kajal Hamidzadeh, Sree Ranjani Ramani, Elizabeth Luis, Irene Tom, [......], Yan Ma, Kiran Mukhyala, Tao Sai, Jiabing Ding, Benjamin Haley, Hooman Shadnia, Sharookh B Kapadia, Lino C Gonzalez, Philip E Hass, Ali A Zarrin
  [show abstract] [hide abstract]
  ABSTRACT: Paired immunoglobulin-like receptor (PILR) α is an inhibitory receptor that recognizes several ligands, including mouse CD99, PILR-associating neural protein, and Herpes simplex virus-1 glycoprotein B. The physiological function(s) of interactions between PILRα and its cellular ligands are not well understood, as are the molecular determinants of PILRα/ligand interactions. To address these uncertainties, we sought to identify additional PILRα ligands and further define the molecular basis for PILRα/ligand interactions. Here, we identify two novel PILRα binding partners, neuronal differentiation and proliferation factor-1 (NPDC1), and collectin-12 (COLEC12). We find that sialylated O-glycans on these novel PILRα ligands, and on known PILRα ligands, are compulsory for PILRα binding. Sialylation-dependent ligand recognition is also a property of SIGLEC1, a member of the sialic acid-binding Ig-like lectins. SIGLEC1 Ig domain shares ∼22% sequence identity with PILRα, an identity that includes a conserved arginine localized to position 97 in mouse and human SIGLEC1, position 133 in mouse PILRα and position 126 in human PILRα. We observe that PILRα/ligand interactions require conserved PILRα Arg-133 (mouse) and Arg-126 (human), in correspondence with a previously reported requirement for SIGLEC1 Arg-197 in SIGLEC1/ligand interactions. Homology modeling identifies striking similarities between PILRα and SIGLEC1 ligand binding pockets as well as at least one set of distinctive interactions in the galactoxyl-binding site. Binding studies suggest that PILRα recognizes a complex ligand domain involving both sialic acid and protein motif(s). Thus, PILRα is evolved to engage multiple ligands with common molecular determinants to modulate myeloid cell functions in anatomical settings where PILRα ligands are expressed.
  Journal of Biological Chemistry 03/2012; 287(19):15837-50. · 4.77 Impact Factor