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


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


J Biol Chem

A molecular switch in mouse cd1d modulates natural killer t cell activation by alpha-galactosylsphingamides

Wang J, Guillaume J, Janssens J, Remesh SG, Ying G, Bitra A, Van Calenbergh S, Zajonc DM
J Biol Chem

Structural basis of NKT cell inhibition using the T-cell receptor-blocking anti-CD1d antibody 1B1

Ying G, Wang J, Mallevaey T, Van Calenbergh S, Zajonc DM
J Biol Chem

Structure of human cytomegalovirus UL144, an HVEM orthologue, bound to the B and T cell lymphocyte attenuator

Bitra A, Nemcovicova I, Picarda G, Doukov T, Wang J, Benedict CA, Zajonc DM
J Biol Chem

Crystal structure of the m4-1BB/4-1BBL complex reveals an unusual dimeric ligand that undergoes structural changes upon 4-1BB receptor binding

Bitra A, Doukov T, Destito G, Croft M, Zajonc DM
Eur J Immunol

Self-glycerophospholipids activate murine phospholipid-reactive T cells and inhibit iNKT cell activation by competing with ligands for CD1d loading

Halder RC, Tran C, Prasad P, Wang J, Nallapothula D, Ishikawa T, Wang M, Zajonc DM, Singh RR
Org Biomol Chem

Enhancing T cell responses and tumour immunity by vaccination with peptides conjugated to a weak NKT cell agonist

Compton BJ, Farrand KJ, Tang CW, Osmond TL, Speir M, Authier-Hall A, Wang J, Ferguson PM, Chan STS, Anderson RJ, Cooney…
J Virol

Restriction of human cytomegalovirus infection by galectin-9

Machala EA, Avdic S, Stern L, Zajonc DM, Benedict CA, Blyth E, Gottlieb DJ, Abendroth A, McSharry BP, Slobedman B

4"-O-alkylated alpha-galactosylceramide analogues as iNKT-cell antigens: synthetic, biological, and structural studies

Janssens J, Bitra A, Wang J, Decruy T, Venken K, van der Eycken J, Elewaut D, Zajonc DM, van Calenbergh S
Cell Rep

High-affinity bent beta2-integrin molecules in arresting neutrophils face each other through binding to ICAMs in cis

Fan Z, Kiosses WB, Sun H, Orecchioni M, Ghosheh Y, Zajonc DM, Arnaout MA, Gutierrez E, Groisman A, Ginsberg MH, Ley K
J Biol Chem

Crystal structures of the human 4-1BB receptor bound to its ligand 4-1BBL reveal covalent receptor dimerization as a potential signaling amplifier

Bitra A, Doukov T, Croft M, and Zajonc DM

Characterization of murine antibody responses to vaccinia virus envelope protein A14 reveals an immunodominant antigen lacking of effective neutralization targets

Meng X, Kaever T, Yan B, Trktman P, Zajonc DM, Peters B, Crotty S, Xiang Y
Nat Immunol

CD1c caves in on lipids

Zajonc DM
Nat Commun

A ligand-specific blockage of the intgrin Mac-1 selectivitely targets pathologic inflammation while maintaining protective host-defense

Wolf D, Anto-Michel N, Blankenbach H, Wiedmann A, Buscher K, Hohmann JD, Lim B, B_uml M, Marki A, Mauler M, Duerschmied…
J Biol Chem

Crystal structure of murine 4-1BB and its interaction with 4-1BBL support a role for galectin-9 in 4-1BB signaling

Bitra A, Doukov T, Wang J, Picarda G, Benedict CA, Croft M, Zajonc DM
J Biol Chem

Structure-function characterization of three human antibodies targeting the vaccinia virus adhesion molecule D8

Matho MH, Schlossman A, Gilchuk IM, Miller G, Mikulski Z, Hupfer M, Wang J, Brita A, Meng X, Xiang Y, Kaever T, Doukov…
J Immunol

Regulatory T cell-mediated suppression of inflammation induced by DR3 signaling is dependent on galectin-9

Madireddi S, Eun SY, Mehta AK, Birta A, Zajonc DM, Niki T, Hirashima M, Podack ER, Schreiber TH, Croft M
PLoS One

Crystal structure of Qa-1a with bound Qa-1 determinant modifier peptide

Ying G, Wang J, Kumar V, Zajonc DM
J Immunol

Autoreactivity to sulfatide by human invariant NKT cells

Stax AM, Tuengel J, Girardi E, Kitano N, Allan LL, Liu V, Zheng D, Panenka WJ, Guillaume J, Wong CH, van Calenbergh S,…
Sci Rep

Galactosylsphingamides: new α-GalCer analogues to probe the F'-pocket of CD1d

Guillaume J, Wang J, Janssens J, Remesh SG, Risseeuw MDP, Decruy T, Froeyen M, Elewaut D, Zajonc DM, Calenbergh SV
J Biol Chem

Unconventional peptide presentation by major histocompatibility complex (MHC) class I allele HLA-A*02:01: breaking confinement

Remesh SG, Andreatta M, Ying G, Kaever T, Nielsen M, McMurtrey C, Hildebrand W, Peters B, Zajonc DM
Cell Death Differ

N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death

Dufour F, Rattier T, Shirley S, Picarda G, Constantinescu AA, Morlé A, Zakaria AB, Marcion G, Causse S, Szegezdi E,…
Subcell Biochem

Antibody recognition of immunodominant vaccinia virus envelope proteins

Zajonc DM

The CD1 family: serving lipid antigens to T cells since the mesozoic era

Zajonc DM

CD1, MR1, NKT, and MAIT: evolution and origins of non-peptidic antigen recognition by T lymphocytes

Zajonc DM, Flajnik MF
J Biol Chem

Structure of an α-helical peptide and lipopeptide bound to the nonclassical major histocompatibility complex (MHC) class I molecule CD1d

Girard E, Wang J, Zajonc DM
J Virol

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

Kaever T, Matho MH, Meng Z, Crickard L, Schlossman A, Xiang Y, Crotty S, Peters B, Zajonc DM
J Biol Chem

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

Girard E, Wang J, Zajonc DM
J Virol

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

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

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

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

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

Birkholz AM, Girardi E, Wingender G, Khurana A, Wang J, Zhao M, Zahner S, Illarionov PA, Wen X, Li M, Yuan W, Porcelli…
Frontiers in Immunology

Recognition of microbial glycolipids by natural killer T cells

Zajonc DM, Girardi E
Journal of Biological Chemistry

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

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

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

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

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

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

Kaever T, Meng X, Matho MH, Schlossman A, Li S, Sela-Culang I, Ofran Y, Buller M, Crump RW, Parker S, Fraizer A, Crotty…
Journal of Experimental Medicine

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

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

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

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

Nemčovičová I, Zajonc DM
Immunology and Cell Biology

A γδ T-cell glimpse of glycolipids

Zajonc D, Girardi E
PLoS One

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

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

Kronenberg M, Zajonc DM
PLoS Pathogens

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

Nemčovičová I, Benedict CA, Zajonc DM
Cell Host & Microbe

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

Smith W, Tomasec P, Aicheler R, Loewendorf A, Nemčovičová I, Wang EC, Stanton RJ, Macauley M, Norris P, Willen L,…
International Immunology

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

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

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

Girardi E, Zajonc DM
PLoS One

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

Wang J, Guillaume J, Pauwels N, Van Calenbergh S, Van Rhijn I, 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

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

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

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

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

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

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

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

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

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

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

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

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

Joyce S, Girardi E, Zajonc DM
EMBO Journal

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

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

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

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

Aspeslagh S, Nemcovic M, Pauwels N, Venken K, Wang J, Van Calenbergh S, Zajonc DM, Elewaut D
Dev Comp Immunol

Conservation of CD1 protein expression patterns in the chicken

Ly N, Danzi NM, Wang J, Zajonc DM, Dascher CC

Principal Investigator

Dirk Zajonc, Ph.D.

Associate Professor

Dr. Zajonc is an Associate Professor at La Jolla Institute. 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

Aruna Bitra, Ph.D.

Postdoctoral Fellow

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 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.

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.