Roy Mariuzza


Mariuzza Group



Call: (240) 314-6243


  • Ph.D., Biochemistry, University of Paris, France, 1986
  • M.S., Biochemistry, Yale University, 1978
  • B.S., Biochemistry, Yale University, 1978


Research in Dr. Roy Mariuzza’s laboratory focuses on understanding how immune system cell surface receptors recognize molecules. Several classes of recognition molecules are under study: antibodies, T cell receptors (TCRs), natural killer (NK) cell receptors, and variable lymphocyte receptors (VLRs). 


T cell recognition of self-antigens in multiple sclerosis

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) driven by autoimmune CD4+ T cells. T cell responses to CNS self-antigens, such as myelin basic protein (MBP), are a critical autoimmune event in MS. To understand how T cells recognize self-antigens, the Mariuzza lab is determining structures of TCRs from MS patients bound to MBP peptides that are bound by MHC class II molecules.

T cell recognition of tumor antigens in human melanoma

Anti-tumor immunity can target non-mutated self-proteins or proteins with tumor-associated mutations or other modifications. The lab is carrying out structural studies using X-ray crystallography to investigate how tumor-specific CD4+ T cells from melanoma patients recognize each of these types of tumor antigens.

Structural basis for recognition of cellular and viral ligands by NK receptors

Natural killer (NK) cells are a first line of defense in immune responses against tumors and virally infected cells. A dynamic balance between activating receptors and inhibitory receptors regulates NK cell function. The lab is investigating the structural basis for NK receptor recognition of cellular and viral ligands using X-ray crystallography, and correlating this information with a better understanding of how NK cells function.

Evolution of the adaptive immune system

The evolutionary origin of adaptive immunity in vertebrates is the subject of much conjecture. The lab is studying the structural underpinnings of this process by defining the antigen recognition properties of newly discovered receptors expressed on the lymphocytes of jawless vertebrates (lamprey and hagfish). Antibodies are composed of Ig domains, but variable lymphocyte receptors (VLRs) consist of leucine-rich repeats. X-ray crystallographic studies of VLRs in complex with protein and carbohydrate antigens are providing unique insights into the diversity of molecular solutions nature has evolved for antigen recognition.

Structure of TCR-pMHC-CD4 complex

Structural analysis of the TCR–CD3 complex and TCR signaling

T cells are able to specifically recognize a peptide on the surface of another cell and then be activated to respond to this interaction. Peptides are short segments of protein molecules bound to a cell surface molecule called MHC. This peptide-MHC complex can engage a specific T cell receptor complex composed of a TCR heterodimer and CD3 molecules. The TCR mediates peptide–MHC (pMHC) recognition, while the CD3 molecules activate signals within the T cell. To understand the mechanism whereby TCR engagement by pMHC initiates signaling, the lab is investigating:  1) the spatial organization of the TCR–CD3 complex; and 2) potential structural changes in the TCR that are relayed to CD3. These studies are being undertaken through a combination of NMR spectroscopy, X-ray crystallography, and cell-based assays.

Structure-based design of hepatitis C vaccine

Hepatitis C virus (HCV) has devised multiple mechanisms of viral escape that contribute to the development of chronic infection. The lab is carrying out structural studies of binding interactions between human monoclonal antibodies and the HCV E2 envelope glycoprotein as well as structure-guided computational modeling to engineer E2 proteins that elicit broadly neutralizing anti-HCV antibodies for testing as vaccine candidates.

CryoEM structure of a therapeutic antibody (favezelimab) bound to human LAG3 determined using a bivalent Fab as fiducial marker.
Structure of engineered hepatitis C virus E1E2 ectodomain in complex with neutralizing antibodies.
Structural insights into protection against a SARS-CoV-2 spike variant by T cell receptor (TCR) diversity.
Structure-Based Design of Potent Iminosugar Inhibitors of Endoplasmic Reticulum α-Glucosidase I with Anti-SARS-CoV-2 Activity.
Cooperative binding of T cell receptor and CD4 to peptide-MHC enhances antigen sensitivity.
Editorial overview: Engineering and design.
Identification of Endoplasmic Reticulum α-Glucosidase I from a Thermophilic Fungus as a Platform for Structure-Guided Antiviral Drug Design.
Induction of broadly neutralizing antibodies using a secreted form of the hepatitis C virus E1E2 heterodimer as a vaccine candidate.
T cell receptors (TCRs) employ diverse strategies to target a p53 cancer neoantigen.
Structural assessment of HLA-A2-restricted SARS-CoV-2 spike epitopes recognized by public and private T-cell receptors.
N-Substituted Valiolamine Derivatives as Potent Inhibitors of Endoplasmic Reticulum α-Glucosidases I and II with Antiviral Activity.
Supramolecular assembly of Toll-like receptor 7/8 agonist into multimeric water-soluble constructs enables superior immune stimulation in vitro and in vivo.
Design of a native-like secreted form of the hepatitis C virus E1E2 heterodimer.
Crystal Structure of a Bivalent Antibody Fab Fragment.
Peptide-MHC Binding Reveals Conserved Allosteric Sites in MHC Class I- and Class II-Restricted T Cell Receptors (TCRs).
Structure-Based Design of Hepatitis C Virus E2 Glycoprotein Improves Serum Binding and Cross-Neutralization.
In Vivo and In Vitro Potency of Polyphosphazene Immunoadjuvants with Hepatitis C Virus Antigen and the Role of Their Supramolecular Assembly.
Structural basis for oligoclonal T cell recognition of a shared p53 cancer neoantigen.
The structural basis of T-cell receptor (TCR) activation: An enduring enigma.
How Natural Killer Cell Receptors Stick to Cell-Cell Adhesion Proteins.