A structural perspective on MHC class Ib molecules in adaptive immunity

Sullivan, Lucy C.; Hoare, Hilary Linda; McCluskey, James; Rossjohn, Jamie; Brööks, Andrëw G.

doi:10.1016/j.it.2006.07.006

Cited by 60 publications

(57 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, the amide group of P2-Met forms a hydrogen bond, which is conserved in most MHC-Ia structures, to the terminal carboxyl oxygen of Glu 63 , whereas Lys 66 N h forms a hydrogen bond to the P2-Met carbonyl group. The N terminus of the peptide is anchored by hydrogen bonds between the P1-Ala and the sidechain hydroxyl groups of Tyr 7 and Tyr 171 that are conserved in MHC class I-peptide structures (Figs. 3, 4A) (48).…”

Section: Peptide-binding Specificitymentioning

confidence: 99%

“…In contrast to MHC-Ia molecules, MHC-Ib molecules, which include HLA-E, HLA-F, and HLA-G in humans and H2-M3 and Qa-1 b in mice, are much less polymorphic and often exhibit a relatively restricted tissue distribution (6,7). This limited polymorphism results in a marked reduction in the diversity of peptides presented by MHC-Ib proteins across the species.…”

mentioning

confidence: 99%

“…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%

See 2 more Smart Citations

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

Sullivan

Vivian

et al. 2012

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Peptide-binding Specificitymentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

Sullivan

Vivian

et al. 2012

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…CTL) [15]. Although non-classical MHC class Ib molecules (class Ib) are often considered to have a more prominent role in innate immunity, their roles in adaptive immunity are becoming more apparent, particularly in response to tumors and pathogens [16]. Some evidence suggests that certain class Ib molecules may play a role in immune recognition of class Ia-low or -negative tumor cells through their interaction with T cell receptors (TCR) of CD8 + ab T cells [17][18][19][20] as well as non-T cell inhibitory or triggering receptors expressed by NK cells and T cells [21][22].…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, the class Ib gene family is generally composed of very heterogeneous genes that have limited tissue distribution, low polymorphism and a lower level of cell surface expression than class Ia [21,23], although there are many exceptions to this definition. In the case of class Ib molecules that bind peptides, their low polymorphism results in a markedly reduced diversity of bound peptides [16]. Phylogenetic analysis of class Ib genes indicates that they have rapidly diversified during evolution and display many species-specific specializations, which complicates the study of their functions [22].…”

Section: Introductionmentioning

confidence: 99%

Involvement of nonclassical MHC class Ib molecules in heat shock protein‐mediated anti‐tumor responses

et al. 2007

View full text Add to dashboard Cite

Nonclassical MHC class Ib (class Ib) genes are found in all jawed vertebrates, and their products are hypothesized to be indicators of intracellular stress and malignancy. They may be involved in immune recognition of classical MHC class Ia (class Ia)‐low or ‐negative tumor cells through their interaction with T cell receptors and/or non‐T cell inhibitory or triggering receptors expressed by NK cells and T cells. In the frog Xenopus, the molecular chaperone gp96 mediates a potent immune response involving antigen‐specific classical class Ia‐unrestricted CD8+ CTL (CCU‐CTL) against a transplantable thymic tumor (15/0) that does not express class Ia molecules. We hypothesized that Xenopus nonclassical class Ib gene products (XNC) are involved in gp96‐mediated CCU‐CTL anti‐tumor responses. To investigate the involvement of class Ib gene products in Xenopus anti‐tumor responses, we generated, for the first time in ectothermic vertebrates, stable tumor transfectants expressing short hairpin RNA (shRNA) to silence either XNC directly or β2m to prevent class Ib surface expression. Both types of 15/0 transfectants are more resistant to CCU‐CTL killing, more tumorigenic and more susceptible to NK‐like cell killing. This study provides in vitro and in vivo evidence of the evolutionary conservation of class Ib involvement in anti‐tumor CD8+ T cell responses.

show abstract

Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA‐E during active tuberculosis and express type 2 cytokines

et al. 2015

Self Cite

View full text Add to dashboard Cite

CD8 T cells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 T cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T cells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules.We show here that CD8 T cells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR αβ mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectable by a significant enhanced ex vivo frequency of tetramer-specific circulating CD8 T cells during active TB. These CD8 T cells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL-dependent cytolytic and microbicidal activity toward M. tuberculosis infected target cells. Our results, together with the finding that HLA-E/M. tuberculosis peptide specific CD8 T cells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T-cell population that participates in immune response in TB.Keywords: CD8 T lymphocytes r HLA-E r Mycobacterium tuberculosis r TB r Tetramers r Type 2 cytokines Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Prof. Francesco Dieli e-mail: francesco.dieli@unipa.it * These authors share first authorship for this work.* * These authors share last authorship for this work. [2]. In humans, M. tuberculosis reactive CD8 T cells recognize peptides associated to classical HLA-A, HLA-B, and HLA-C class I (class Ia) molecules, glycolipids associated to group 1 CD1 molecules [5,6], and mycobacterial Ag associated to MHC class I related molecule (MR1) [7]. However, there is little information on the role that these cells play during infection. In mice, the MHC class Ib molecule H2-M3 binds formylated peptides derived from M. tuberculosis and induces H2-M3-restricted CD8 T cells [8,9] that are protective against M. tuberculosis infection [10]. In humans, CD8 T cells restricted by class Ib molecules comprise the very large majority of the overall M. tuberculosis specific CD8 T-cell response [11] and CD8 T cells recognizing M. tuberculosis Ags in the context of the class Ib molecule HLA-E have been isolated from subjects with latent M. tuberculosis infection [12,13]. However, the functions of this HLA-E-restricted population, as well as its contribution to the host response to M. tuberculosis during infection and disease, remain unknown.HLA-E is the least polymorphic of all the HLA molecules [14] with only two alleles in the Caucasian population, which differ at one aa position located outside the peptidebinding groove [15]. Physiologically, HLA-E binds nonamer peptides derived from the signal sequence of other HLA class I molecules [16,17], a...

show abstract

A structural perspective on MHC class Ib molecules in adaptive immunity

Cited by 60 publications

References 71 publications

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

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

Involvement of nonclassical MHC class Ib molecules in heat shock protein‐mediated anti‐tumor responses

Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA‐E during active tuberculosis and express type 2 cytokines

Contact Info

Product

Resources

About