Zajonc Lab

Zajonc Lab

"Crystallography enables us to see a single atom in the highest resolution now in existence. Having this detailed, structured image is a significant advantage in combating disease because it’s easier to stop what you can see." — Dirk Zajonc, Ph.D. // Associate Professor
Division of Cellular Biology

Overview

Our group is primarily interested in understanding the relationship between the three-dimensional structure of a protein and its function. The immune system is the perfect system for those studies as it has acquired the ability to virtually interact with any pathogen that it encounters. We are particularly interested how microbial lipids, which are chemically different from our own are recognized by T cells. Using that knowledge, we are trying to change the chemical structure of lipids to alter both the quality and the magnitude of the associated immune response. On the flip side, we are also looking at the immune system from the microbe’s point-of-view. How can the microbe evade immune recognition? To this end, we are studying the structure and function of viral immunomodulatory proteins. One of those proteins, UL141 from human cytomegalovirus has the ability to bind and inhibit at least two different proteins of the immune system, which differ substantially in their three-dimensional structures.

From The Lab

Mar 13, 2013

Researchers advance fight against leading infectious cause of congenital birth defects

Zajonc Lab

Publications

J Biol Chem

Structure of an _-helical peptide and lipopeptide bound to the non-classical MHC class I module DC1d

2016-02
Girard E, Wang J, Zajonc DM
J Virol

Linear epitopes in A27 are targets of protective antibodies induced by vaccination against smallpox

2016-02
Kaever T, Matho MH, Meng Z, Crickard L, Schlossman A, Xiang Y, Crotty S, Peters B, Zajonc DM
eLIFE

Toxoplasma gondii peptide ligands open the gate of the HLA class I binding groove

2016-01
McMurtrey C, Trolle T, Sansom T, Remesh SG, Kaever T, Bardet W, Jackson K, McLeod R, Sette A, Nielsen M, Zajonc DM,…
PLoS Pathogens

Structural and functional characterization of anti-A33 antibodies reveal a potent cross-species orthopoxviruses neutralizer

2015-09
Matho MH, Schlossman A, Meng X, Benhnia MR, Kaever T, Buller M, Doronin K, Parker S, Peters B, Crotty S, Xiang Y,…
Journal of Immunology

A novel glycolipid antigen for NKT cells that preferentially induces IFN-γ production

2015-08
Birkholz AM, Girardi E, Wingender G, Khurana A, Wang J, Zhao M, Zahner S, Illarionov PA, Wen X, Li M, Yuan W, Porcelli…
Journal of Biological Chemistry

Lipid and carbohydrate modifications of α-galactosylceramide differently influence mouse and human type I natural killer T cell activation

2015-07
Birkholz A, Nemčovič M, Yu ED, Girardi E, Wang J, Khurana A, Pauwels N, Farber E, Chitale S, Franck RW, Tsuji M,…
Bioorganic & Medicinal Chemistry

Synthesis of C-5" and C-6"-modified α-GalCer analogues as iNKT-cell agonists

2015-07
Guillaume J, Pauwels N, Aspeslagh S, Zajonc DM, Elewaut D, Van Calenbergh S
Mucosal Immunology

Unique lamina propria stromal cells imprint the functional phenotype of mucosal dendritic cells

2015-01
Vicente-Suarez I, Larange A, Reardon C, Matho M, Feau S, Chodaczek G, Park Y, Obata Y, Gold R, Wang-Zhu Y, Lena C,…
PLoS Pathogens

Murine anti-vaccinia virus D8 antibodies target different epitopes and differ in their ability to block D8 binding to CS-E

2014-12
Matho MH, de Val N, Miller GM, Brown J, Schlossman A, Meng X, Crotty S, Peters B, Xiang Y, Hsieh-Wilson LC, Ward AB,…
Journal of Immunology

Recognition of lysophosphatidylcholine by type II NKT cells and protection from an inflammatory liver disease

2014-11
Maricic I, Girardi E, Zajonc DM, Kumar V
Journal of Virology

Potent neutralization of vaccinia virus by divergent murine antibodies targeting a common site of vulnerability in L1 protien

2014-10
Kaever T, Meng X, Matho MH, Schlossman A, Li S, Sela-Culang I, Ofran Y, Buller M, Crump RW, Parker S, Fraizer A, Crotty…
Immunity

The identification of the endogenous ligands of natural killer T cells reveals the presence of mammalian α-linked glycosylceramides

2014-10
Kain L, Webb B, Anderson BL, Deng S, Holt M, Constanzo A, Zhao M, Self K, Teyton A, Everett C, Kronenberg M, Zajonc DM,…
Journal of Experimental Medicine

Galectin-9 controls the therapeutic activity of 4-1BB-targeting antibodies

2014-06
Madireddi S, Eun SY, Lee SW, Nemcovicova I, Mehta AK, Zajonc DM, Nishi N, Niki T, Hirashima M, Croft M
Structure

Using a combined computational-exterimental approach to predict antibody-specific B cell epitopes

2014-04
Sela-Culang I, Benhnia MR, Matho MH, Kaever T, Maybeno M, Scholossman A, Nimrod G, Li S, Ziang Y, Zajonc D, Crotty S,…
Acta Ctystallographica Section D-Biological Crystallography

The structure of cytomeglaovirus immune modulator UL141 highlights structural lg-fold versatility for receptor binding

2014-03
Nemčovičová I, Zajonc DM
Immunology and Cell Biology

A γδ T-cell glimpse of glycolipids

2014-02
Zajonc D, Girardi E
PLoS One

Helicobacter pylori cholesteryl α-glucosides contribute to its pathogenicity and immune response by natural killer T cells

2013-12
Ito Y, Vela JL, Matsumura F, Hoshino H, Tsynik A, Lee H, Girardi E, Zajonc DM, Liddington R, Kobayashi M, Bao X,…
Nature Immunology

A 'GEM' of a cell

2013-06
Kronenberg M, Zajonc DM
PLoS Pathogens

Structure of human cytomegalovirus UL141 binding to TRAIL-R2 reveals novel, non-canonical death receptor interactions

2013-03
Nemčovičová I, Benedict CA, Zajonc DM
Cell Host & Microbe

Human cytomegalovirus glycoprotein UL141 targets the TRAIL death receptors to thwart host innate antiviral defenses

2013-03
Smith W, Tomasec P, Aicheler R, Loewendorf A, Nemčovičová I, Wang EC, Stanton RJ, Macauley M, Norris P, Willen L,…
Journal of Virology

Unusual features of vaccinia virus extracellular virion form neutralization resistance revealed in human antibody responses to the smallpox vaccine

2013-02
Benhnia MR, Maybeno M, Blum D, Aguilar-Sino R, Matho M, Meng X, Head S, Felgner PL, Zajonc DM, Koriazova L, Kato S,…
International Immunology

The bovine CD1D gene has an unusual gene structure and is expressed by cannot present alpha-galactosylceramide with a C26 fatty acid

2013-02
Nguyen TK, Koets AP, Vordermeler M, Jervis PJ, Cox LR, Graham SP, Santema WJ, Moody DB, van Calenbergh S, Zajonc DM,…
British Journal of Haematology

Phage display generation of a novel human anti-CD1A monoclonal antibody with potent cytolytic activiry

2012-11
Bechan GI, Lee DW, Zajonc DM, Heckel D, Xian R, Throsby M, van Meijer M, Germeraad WT, Kruisbeek AM, Egeler RM, Arceci…
Immunological Reveiws

Molecular basis of lipid antigen presentationby CD1d and recognition by natural killer T cells

2012-11
Girardi E, Zajonc DM
Nature Immunology

Type II natural killer T cells use features of both innate-like and conventional T cells to recognize sulfatide self antigens

2012-09
Girardi E, Maricic I, Wang J, Mac TT, Iyer P, Kimar V, Zajonc DM
Journal of Virology

Structural and biochemical characterization of the vaccinia virus envelope protein D8 and its recognition by the antibody LA5

2012-08
Matho MH, Maybeno M, Benhnia MR, Becker D, Meng X, Xiang Y, Crotty S, Peters B, Zajonc DM
Proceedings of the National Academy of Sciences of the United States of America

Atomic structure of the autosomal recessive hypercholesterolemia phosphotyrosine-binding domain in complex with the LDL-receptor tail

2012-05
Dvir H, Shah M, Girardi E, Guo L, Farquhar MG, Zajonc DM
Annals of the New York Academy of Sciences

Interplay between carbohydrate and lipid in recognition of glycolipid antigens by natural killer T cells

2012-04
Pei B, Vela JL, Zajonc D, Kronenberg M
Journal of Immunology

Structural and functionlal characterization of a novel nonglycosidic type 1 NKT agonist with immunomodulatory properties

2012-03
Kerzerho J, Yu ED, Barra CM, Alari-Pahisa E, Girardi E, Harrak Y, Lauzurica P, Llebaria A, Zajonc DM, Akbari O,…
Journal of Clinical Investigation

Histamine-releasing factor has a proinflammatory role in mouse models of asthma and allergy

2012-01
Kashiwakura JC, Ando T, Matsumoto K, Kimura M, Kitaura J, Matho MH, Zajonc DM, Ozeki T, Ra C, MacDonald SM, Siraganian…
Journal of Biological Chemistry

Structural basis for the recognition of C20:2-αGalCer by the invariant natural killer T cell receptor-like antibody L363

2012-01
Yu ED, Griardi E, Wang J, Mac TT, Yu KO, Van Calenbergh S, Procelli SA, Zajonc DM
Chemistry & Biology

Glycolipids that elicit IFN-biased responses from natural killer T cells

2011-12
Tyznik AJ, Farber E, Girardi E, Birkholz A, Li Y, Chitale S, So R, Arora P, Khurana A, Wang J, Porcelli SA, Zajonc DM,…
Organic & Biomolecular Chemistry

Divergent synthetic approach to a 6"-modified α-GalCer analogues

2011-12
Pauwels N, Aspeslagh S, Vanhoenacker G, Sandra K, Yu ED, Zajonc DM, Elewaut D, Linclau B, Van Calenbergh S
PLoS Biology

Unique interplay between sugar and lipid in determining the antigenic potency of bacterial antigens for NKT cells

2011-11
Girardi E, Yu ED, Li Y, Tarumoto N, Pei B, Wang J, Illarionov P, Kinjo Y, Kronenberg M, Zajonc DM
Nature Immunology

Invariant natural killer T cells recognize glycolipids from pathogenic gram-positive bacteria

2011-09
Kinjo Y, Illarionov P, Vela JL, Pei B, Girardi E, Li X, Li Y, Imamura M, Kaneko Y, Okawara A, Miyazaki Y, Gomez-Velasco…
Journal of Immunology

Cutting edge: structural basis for the recognition of β-linked glycolipid antigens by invariant NKT cells

2011-09
Yu ED, Girardi E, Wang J, Zajonc DM
Journal of Immunology

NKT cell ligand recognition logic: molecular basis for a synaptic duet and transmission of inflammatory effectors

2011-08
Joyce S, Girardi E, Zajonc DM
EMBO Journal

Galactose-modified iNKT cell agonists stabalized by an induced fit of CD1d prevent tumour metastasis

2011-06
Aspeslagh S, Li Y, Yu ED, Pauwels N, Trappeniers M, Girardi E, Decruy T, van Beneden K, Vanken K, Drennan M, Laybaert…
Journal of Immunology

Cardiolipin binds to CD1d and stimulates CD1d-restricted gd T cells in the normal murine repertoireCardiolipin binds to CD1d and stimulates CD1d-restricted gd T cells in the normal murine repertoireCardiolipin binds to CD1d and stimulates CD1d-restricted gd T cells in the normal murine repertoireCardiolipin binds to CD1d and stimulates CD1d-restricted gd T cells in the normal murine repertoireCardiolipin binds to CD1d and stimulates CD1d-restricted gd T cells in the normal murine repertoire

2011-04
Dieude M, Striegl H, Tyznik AJ, Wang J, Behar SM, Piccirillo CA, Levine JS, Zajonc DM, Rauch J
Nucleic Acids Research

IEDB-3D: structural data within the immune epitope database

2011-01
Ponomarenko J, Papangelopoulos N, Zajonc DM, Peters B, Sette A, Bourne PE
Journal of Immunology

Enhanced TCR footrpint by a novel glycolipid increases NKT-dependent tumor protection

0213-09
Aspeslagh S, Nemcovic M, Pauwels N, Venken K, Wang J, Van Calenbergh S, Zajonc DM, Elewaut D
PLoS One

Crystal structures of bovine CD1d reveal altered αGalCer presentation and a restricted A' pocket unable to bind long-chain glycolipids

2016-07
Wang J, Guillaume J, Pauwels N, Van Calenbergh S, Van Rhijn I, Zajonc DM

Principal Investigator

zajonc

Dirk Zajonc, Ph.D.

Associate Professor

Dr. Zajonc is an Associate Professor in the Division of Cell Biology. Dr. Zajonc and his team determine the three-dimensional structures of immune system proteins at the atomic level using protein crystallography.

Dr. Zajonc received his M. Sc from the University of Erlangen-Nuremberg (Germany) in 1998 and his Ph. D. in biochemistry in 2001. He completed his postdoctoral training at the Scripps Research Institute in 2006. Dr. Zajonc received an Investigator award from the Cancer Research institute in 2007.

Dr. Zajonc is an Editorial Board Member for two newly established open-access journals, Lipid Insights and Glycobiology Insights.

Lab Members

SAMSUNG CAMERA PICTURES

Aruna Bitra, Ph.D.

Postdoctoral Fellow

Biosketch:
I graduated from the Indian Institute of Technology in Bombay, India in 2014 with a PhD. I began working as a postdoc in the Zajonc laboratory at the La Jolla Institute for Allergy and Immunology in 2015.

Research Focus:
My research mainly focuses on the structural and biochemical characterization of the interaction between TNF receptors and their binding partners, including TNF ligands and Galectins, to promote signaling.

Jing Wang

Lab Manager

Biosketch:
I graduated from Shandong University (Jinan, China) in 2000 with a master degree of Microbiology. After graduation, I worked in China Agricultural University (Beijing, China) as a lecturer/Assistant Professor until 2005. I was a visiting scientist in the Laboratory of Microbiology, Wageningen University, the Netherlands in 2005. I moved to San Diego in 2006 where I assisted in setting up the Zajonc lab at LJI.

Job Duties:
I am fully trained in all current lab techniques and a key person in producing a variety of different recombinant proteins, such as CD1 and TCR’s that are used throughout the lab. I assess the loading levels of different glycolipid analogs to CD1d and determine the binding kinetics of different TCR’s to CD1d-glycolipid complexes using Surface Plasmon Resonance. Using cell-based assay, I determine the potency of the various lipids in activation T cell hybridomas and crystallize CD1d-glycolipid and CD1d-glycolipid TCR complexes for subsequent structure determination.

As a lab manager, I am responsible for training new research technicians, maintaining the lab equipment and work area in a safe, clean and organized condition.

I also assist new personnel, especially new postdoctoral scientists to get their research up and running.

Ge Ying

Visiting Scientist

Zajonc Lab

Research Projects

Structural biology creates a detailed, high-resolution view of the shape of the proteins that arm our immune system and how they interact with other proteins or bits and pieces of an invading pathogen. Combine that with the study of the immune response that follows this initial interaction and the possibilities are endless.