Biomedical subjects

Hilary L Hoare

Publications and source records attributed to Hilary L Hoare.

3 recordsLinked to original sources

PubMed2006

A structural perspective on MHC class Ib molecules in adaptive immunity.

The highly polymorphic MHC class Ia molecules have a central role in adaptive immunity. By contrast, the closely related MHC class Ib molecules, which show limited polymorphism, are best known for regulating innate immune responses. Nevertheless, a recent area of interest is the emerging role of class Ib molecules in adaptive immunity, particularly in response to tumours and pathogens such as Mycobacteria, Listeria and Salmonella. Here, we review recent findings in this area, highlighting the structure of a T-cell receptor complexed with a cytomegalovirus peptide bound to the class Ib molecule, HLA-E. Collectively, these findings have implications for immunity, transplantation and autoimmunity, and our understanding of the evolution and plasticity of the molecular interactions mediating adaptive immunity.

Animals↗

PubMed2006

Structural basis for a major histocompatibility complex class Ib-restricted T cell response.

In contrast to antigen-specific immunity orchestrated by major histocompatibility complex (MHC) class Ia molecules, the ancestrally related nonclassical MHC class Ib molecules generally mediate innate immune responses. Here we have demonstrated the structural basis by which the MHC class Ib molecule HLA-E mediates an adaptive MHC-restricted cytotoxic T lymphocyte response to human cytomegalovirus. Highly constrained by host genetics, the response showed notable fine specificity for position 8 of the viral peptide, which is the sole discriminator of self versus nonself. Despite the evolutionary divergence of MHC class Ia and class Ib molecules, the structure of the T cell receptor-MHC class Ib complex was very similar to that of conventional T cell receptor-MHC class Ia complexes. These results emphasize the evolutionary 'ambiguity' of HLA-E, which not only interacts with innate immune receptors but also has the functional capacity to mediate virus-specific cytotoxic T lymphocyte responses during adaptive immunity.

Animals↗

PubMed2005

Crystal structure of HLA-G: a nonclassical MHC class I molecule expressed at the fetal-maternal interface.

HLA-G is a nonclassical major histocompatibility complex class I (MHC-I) molecule that is primarily expressed at the fetal-maternal interface, where it is thought to play a role in protecting the fetus from the maternal immune response. HLA-G binds a limited repertoire of peptides and interacts with the inhibitory leukocyte Ig-like receptors LIR-1 and LIR-2 and possibly with certain natural killer cell receptors. To gain further insights into HLA-G function, we determined the 1.9-A structure of a monomeric HLA-G complexed to a natural endogenous peptide ligand from histone H2A (RIIPRHLQL). An extensive network of contacts between the peptide and the antigen-binding cleft reveal a constrained mode of binding reminiscent of the nonclassical HLA-E molecule, thereby providing a structural basis for the limited peptide repertoire of HLA-G. The alpha3 domain of HLA-G, a candidate binding site for the LIR-1 and -2 inhibitory receptors, is structurally distinct from the alpha3 domains of classical MHC-I molecules, providing a rationale for the observed affinity differences for these ligands. The structural data suggest a head-to-tail mode of dimerization, mediated by an intermolecular disulfide bond, that is consistent with the observation of HLA-G dimers on the cell surface.

Amino Acid Sequence↗