A5056271795- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- Analytical Chemistry and Chromatography
- Blood Coagulation and Thrombosis Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Synthesis and Characterization of Heterocyclic Compounds
- Psoriasis: Treatment and Pathogenesis
- Synthesis and Reactions of Organic Compounds
- Immune Response and Inflammation
- CAR-T cell therapy research
- Diabetes and associated disorders
- Synthesis and biological activity
- Fibroblast Growth Factor Research
- Cancer Immunotherapy and Biomarkers
- vaccines and immunoinformatics approaches
- Silicone and Siloxane Chemistry
- Protein Tyrosine Phosphatases
- Cytomegalovirus and herpesvirus research
- Computational Drug Discovery Methods
- Reproductive System and Pregnancy
- Respiratory viral infections research
- Influenza Virus Research Studies
Stanford University
2007-2021
Pfizer (United States)
2016-2018
Pfizer (United Kingdom)
2018
Monash University
2003-2010
Howard Hughes Medical Institute
2009
The University of Melbourne
2004
HLA-B*4402 and B*4403 are naturally occurring MHC class I alleles that both found at a high frequency in all human populations, yet they only differ by one residue on the alpha2 helix (B*4402 Asp156-->B*4403 Leu156). CTLs discriminate between B*4403, these allotypes stimulate strong mutual allogeneic responses reflecting their known barrier to hemopoeitic stem cell transplantation. Although share >95% of peptide repertoire, presents more unique peptides than B*4402, consistent with stronger...
The CD3εγ heterodimer is essential for expression and function of the T cell receptor. crystal structure human described to 2.1-Å resolution complexed with OKT3, a therapeutic mAb that not only activates tolerizes mature cells but also induces regulatory cells. mode dimerization provides general structural basis CD3 assembly maps candidate antigen receptor docking sites, including duplicated linear region rich in acidic residues unique CD3ε. OKT3 binds an atypically small area CD3ε has low...
HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that also controls the choice of Ag presentation pathway. A single amino acid distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits to constitutively acquire peptides without any detectable incorporation into transporter associated with (TAP)-associated peptide loading complex even under conditions extreme starvation. This mode capture is less susceptible viral interference than...
Human leukocyte antigen (HLA) gene polymorphism plays a critical role in protective immunity, disease susceptibility, autoimmunity, and drug hypersensitivity, yet the basis of how HLA influences T cell receptor (TCR) recognition is unclear. We examined natural micropolymorphism HLA-B44, an important large allelic family, affected recognition. cell–mediated immunity to Epstein-Barr virus determinant (EENLLDFVRF) enhanced when HLA-B*4405 was presenting allotype compared with HLA-B*4402 or...
T cells specific for the cytochrome c Ag are widely used to investigate many aspects of TCR specificity and interactions with peptide-MHC, but structural information has long been elusive. In this study, we present structures well-studied 2B4 TCR, as well a naturally occurring variant 5c.c7 226, which is cross-reactive more than half possible substitutions at all three TCR-sensitive residues on peptide Ag. These alone in complex peptide-MHC ligands allow us reassess prior mutagenesis...
Residues within processed protein fragments bound to major histocompatibility complex class I (MHC-I) glycoproteins have been considered function as a series of “independent pegs” that either anchor the peptide (p) MHC-I and/or interact with spectrum αβ-T-cell receptors (TCRs) specific for pMHC-I epitope in question. Mining extensive structural database established many self- and viral peptides show direct interresidue interactions, an unexpected finding has led us idea “constrained”...
A noneffector, active site–dependent human IgG1 specific to factor XIa inhibits thrombus formation in two animal models at clinically relevant doses without a detectable effect on hemostasis.
The underlying basis of major histocompatibility complex (MHC) restriction is unclear. Nevertheless, current data suggest that a common thermodynamic signature dictates αβ T cell receptor (TcR) ligation. To evaluate whether this defines MHC restriction, we have examined the highly characterized immunodominant TcR interacting with its cognate peptide–MHC-I ligand. Surprisingly, observed interaction to be governed by favorable enthalpic and entropic forces, which in contrast prevailing...
Abstract Alloreactive T lymphocytes are central mediators of graft-versus-host disease and allograft rejection. A public CTL clonotype with specificity for the alloantigens HLA-B*4402 B*4405 is often expanded to large numbers in healthy HLA-B*0801+ individuals, driven by cross-reactive stimulation common, persistent herpesvirus EBV. Since such alloreactive memory expansions have potential influence transplantation outcome, altered peptide ligands (APLs) target HLA-B*0801-binding EBV peptide,...
Abstract Background Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic 16–amino acid cyclic peptide form naturally occurring C-terminal fragment human growth hormone with therapeutic efficacy against influenza. Shorter linear peptides typically easier to manufacture formulate for delivery than larger peptides. A 6–amino LAT8881, LAT9997, was investigated as potential therapy. Methods LAT9997 evaluated its limit...