Diverse roles of non-diverse molecules: MHC class Ib molecules in host defense and control of autoimmunity

Hofstetter, Amelia R.; Sullivan, Lucy C.; Lukacher, Aron E.; Brööks, Andrëw G.

doi:10.1016/j.coi.2010.09.009

Cited by 29 publications

(28 citation statements)

References 70 publications

(61 reference statements)

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“…In humans, MHC-Ib molecules play a more prominent role in innate immunity, although they can also stimulate adaptive immune responses (6,7,14). For example, HLA-G has been reported to regulate NK cell activation (15,16), whereas HLA-E also regulates the activation of NK cells by acting as a ligand for the *Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Science, Monash University, Clayton, Victoria 3800, Australia; and † Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia CD94-NKG2 receptors (17,18).…”

mentioning

confidence: 99%

A Structural Basis for Antigen Presentation by the MHC Class Ib Molecule, Qa-1b

Sullivan

Vivian

et al. 2012

The Journal of Immunology

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The primary function of the monomorphic MHC class Ib molecule Qa-1b is to present peptides derived from the leader sequences of other MHC class I molecules for recognition by the CD94-NKG2 receptors expressed by NK and T cells. Whereas the mode of peptide presentation by its ortholog HLA-E, and subsequent recognition by CD94-NKG2A, is known, the molecular basis of Qa-1b function is unclear. We have assessed the interaction between Qa-1b and CD94-NKG2A and shown that they interact with an affinity of 17 μM. Furthermore, we have determined the structure of Qa-1b bound to the leader sequence peptide, Qdm (AMAPRTLLL), to a resolution of 1.9 Å and compared it with that of HLA-E. The crystal structure provided a basis for understanding the restricted peptide repertoire of Qa-1b. Whereas the Qa-1b-AMAPRTLLL complex was similar to that of HLA-E, significant sequence and structural differences were observed between the respective Ag-binding clefts. However, the conformation of the Qdm peptide bound by Qa-1b was very similar to that of peptide bound to HLA-E. Although a number of conserved innate receptors can recognize heterologous ligands from other species, the structural differences between Qa-1b and HLA-E manifested in CD94-NKG2A ligand recognition being species specific despite similarities in peptide sequence and conformation. Collectively, our data illustrate the structural homology between Qa-1b and HLA-E and provide a structural basis for understanding peptide repertoire selection and the specificity of the interaction of Qa-1b with CD94-NKG2 receptors.

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mentioning

confidence: 99%

A Structural Basis for Antigen Presentation by the MHC Class Ib Molecule, Qa-1b

Sullivan

Vivian

et al. 2012

The Journal of Immunology

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“…CD1 presentation allows NKT cells to respond to glycolipids from a variety of microorganisms (Zeisseg and Blumberg, 2011). It also appears that the repertoire of lipids presented naturally by CD1d may alter following immune stimulation (reviewed in Hofstetter et al, 2011). Different lipid antigens may be recognised by different subsets of NKT cells.…”

Section: Cd1mentioning

confidence: 99%

“…MR1 engages receptors on MAIT, as described above (reviewed in Hofstetter et al, 2011). These innate lymphocytes take their name from their predominant location in the intestinal lamina propria but can also be found in the circulation.…”

Section: Mr1mentioning

confidence: 99%

Non‐Classical MHC Class I Molecules ( MHC ‐Ib)

Allen

Hogan

2013

Encyclopedia of Life Sciences

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Major histocompatibility complex class I (MHC‐I) molecules are a family of structurally related proteins that were first characterised through their central role in adaptive immunity. Classical MHC class I (MHC‐Ia) molecules comprise a heavy chain complexed with β 2 m to display short peptide fragments on the surface of all nucleated cells. As antigen‐presenting proteins, the classical role of MHC‐Ia is to present these peptides for recognition by T‐cell receptors expressed by cytotoxic T‐cells. MHC‐Ia are also recognised by innate immune receptors on other leukocyte subsets. A diverse group of structurally related proteins, collectively termed nonclassical MHC class I molecules or MHC‐Ib, exists to perform a range of alternative immune roles. Here, the authors describe the biology of human MHC‐Ib molecules and their recognition as antigen‐presenting and antigen‐independent ligands for various immune receptors. Key Concepts: Classical MHC class I (MHC‐Ia) are highly polymorphic proteins which, together with β 2 m, form a structure that presents short peptide antigens for recognition by the classical αβ T‐cell receptor (TCR) on CD8+ T‐cells. MHC‐Ia proteins also exist in nonclassical forms – MHC‐I heavy chain structures lacking β 2 m are found on the surface of activated immune cells, where they are recognised by alternative immune receptors such as members of the leukocyte Ig‐like (LILR) family. Nonclassical MHC‐Ib are usually nonpolymorphic and tend to show a more restricted pattern of expression than their MHC‐Ia counterparts. MHC‐Ib may be recognised by specific subsets of T‐cell receptors or by innate immune receptors. Owing to their recognition by a more restricted set of receptors, MHC‐Ib are able to elicit a rapid response from immune cells and are, therefore, regarded as part of the innate immune system. Some MHC‐Ib act as antigen presenting structures, whereas others are recognised as direct ligands for immune receptors.

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“…However, the involvement of nonclassical MHC class Ib (class Ib) molecules in allorecognition has not been addressed. Class Ib genes in comparison to class Ia are heterogeneous genes with a limited tissue distribution and low polymorphism (Hofstetter, Sullivan et al 2011). Both class Ia and most class Ib molecules have similar structure and need to associate with 2-m in order to be presented at the cells surface (Goyos, Guselnikov et al 2007).…”

Section: Possible Role Of Nonclassical Mhc Class Ib Genes In Skin Tramentioning

confidence: 99%