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Your search keyword '"Mandvi Bharadwaj"' showing total 2 results
Start Over Author "Mandvi Bharadwaj" Journal journal of experimental medicine
2 results on '"Mandvi Bharadwaj"'

1. A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition

Author

Natalie A. Borg, Dale I. Godfrey, James McCluskey, Mandvi Bharadwaj, Nicholas A. Williamson, Lyudmila Kostenko, Gurdyal S. Besra, Lars Kjer-Nielsen, Jamie Rossjohn, Travis Clarke Beddoe, Daniel G. Pellicci, Mark J. Smyth, Hugh H. Reid, and Craig Steven Clements

Subjects
Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, T cell, Immunology, Antigen presentation, CD1, chemical and pharmacologic phenomena, Biology, Article, Antigens, CD1, Mice, Structure-Activity Relationship, 03 medical and health sciences, 0302 clinical medicine, Glycolipid, Species Specificity, Antigen, medicine, Animals, Humans, Immunology and Allergy, Protein Structure, Quaternary, 030304 developmental biology, Antigen Presentation, 0303 health sciences, T-cell receptor, hemic and immune systems, Articles, Natural killer T cell, Protein Structure, Tertiary, Cell biology, Killer Cells, Natural, carbohydrates (lipids), medicine.anatomical_structure, Biochemistry, Structural Homology, Protein, CD1D, Genes, T-Cell Receptor beta, biology.protein, lipids (amino acids, peptides, and proteins), Glycolipids, Genes, T-Cell Receptor alpha, Protein Binding, 030215 immunology
Abstract

Little is known regarding the basis for selection of the semi-invariant alphabeta T cell receptor (TCR) expressed by natural killer T (NKT) cells or how this mediates recognition of CD1d-glycolipid complexes. We have determined the structures of two human NKT TCRs that differ in their CDR3beta composition and length. Both TCRs contain a conserved, positively charged pocket at the ligand interface that is lined by residues from the invariant TCR alpha- and semi-invariant beta-chains. The cavity is centrally located and ideally suited to interact with the exposed glycosyl head group of glycolipid antigens. Sequences common to mouse and human invariant NKT TCRs reveal a contiguous conserved "hot spot" that provides a basis for the reactivity of NKT cells across species. Structural and functional data suggest that the CDR3beta loop provides a plasticity mechanism that accommodates recognition of a variety of glycolipid antigens presented by CD1d. We propose a model of NKT TCR-CD1d-glycolipid interaction in which the invariant CDR3alpha loop is predicted to play a major role in determining the inherent bias toward CD1d. The findings define a structural basis for the selection of the semi-invariant alphabeta TCR and the unique antigen specificity of NKT cells.

Published
2006

2. Natural HLA Class I Polymorphism Controls the Pathway of Antigen Presentation and Susceptibility to Viral Evasion

Author

Tanya Crockford, D. Zernich, Lauren Kate Ely, Rhonda Holdsworth, Andrew G. Brooks, Jamie Rossjohn, Brian D. Tait, Lars Kjer-Nielsen, W.A. Macdonald, Nihay Laham, Mandvi Bharadwaj, James McCluskey, Linus Chang, Chen Au Peh, Nicole A. Mifsud, Anthony W. Purcell, Travis Clarke Beddoe, and Stephen P. Bottomley

Subjects
Models, Molecular, Protein Conformation, Ag presentation, Immunology, Antigen presentation, Genes, MHC Class I, Immunoglobulins, Peptide, Immunogenetics, Human leukocyte antigen, Biology, Crystallography, X-Ray, Article, Antiporters, polymorphism, Cell Line, Mice, 03 medical and health sciences, tapasin, 0302 clinical medicine, Tapasin, HLA-B Antigens, Animals, Humans, Protein Isoforms, Simplexvirus, Immunology and Allergy, Viral Interference, immune evasion, 030304 developmental biology, chemistry.chemical_classification, Genetics, Antigen Presentation, 0303 health sciences, Polymorphism, Genetic, Membrane Transport Proteins, Herpes Simplex, HLA, chemistry, biology.protein, Disease Susceptibility, Antibody, Peptides, 030215 immunology
Abstract

HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion.

Published
2004

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