HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C

Braud, Véronique M.; Allan, David; O’Callaghan, Christopher A.; Söderström, Kalle; D’Andrea, Annalisa; Ogg, Graham S.; Lazetic, Sasha; Young, N. J.; Bell, John I.; Phillips, Joseph H.; Lanier, Lewis L.; McMichael, Andrew J.

doi:10.1038/35869

Cited by 1,981 publications

(1,627 citation statements)

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“…Finally, the affinity might be too low to detect binding, by analogy with the interaction of CD8 with most MHC class I tetramers. It is clear, however, that some NK receptor–class I interactions have a higher affinity 32 33 34 47 48. Further experiments will be required to uncover the basis for this CD1d-mediated inhibition of NK cells.…”

Section: Discussionmentioning

confidence: 99%

“…Tetramers have been used widely to obtain a detailed analysis of the distribution and frequency of conventional CD4 + and CD8 + antigen-specific T cells during a variety of immune responses. Multimers also have been instrumental in identifying the receptors for nonclassical class I molecules such as HLA-E 32, Qa-1 b 33 34, and HLA-G 35. There have been no previous reports, however, of the formation of multimeric antigen-presenting molecules loaded with a lipid antigen.…”

Section: Introductionmentioning

confidence: 99%

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Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers

Matsuda

Naidenko

Gapin

et al. 2000

The Journal of Experimental Medicine

814

823

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A major group of natural killer (NK) T cells express an invariant Vα14+ T cell receptor (TCR) specific for the lipoglycan α-galactosylceramide (α-GalCer), which is presented by CD1d. These cells may have an important immune regulatory function, but an understanding of their biology has been hampered by the lack of suitable reagents for tracking them in vivo. Here we show that tetramers of mouse CD1d loaded with α-GalCer are a sensitive and highly specific reagent for identifying Vα14+ NK T cells. Using these tetramers, we find that α-GalCer–specific T lymphocytes are more widely distributed than was previously appreciated, with populations of largely NK1.1− but tetramer-binding T cells present in the lymph nodes and the intestine. Injection of α-GalCer leads to the production of both interferon γ and interleukin 4 by nearly all NK T cells in the liver and the majority of the spleen within 2 h. These cells mostly disappear by 5 h, and they do not reappear after 1 wk. Curiously, tetramer-positive thymocytes do not rapidly synthesize cytokines, nor do they undergo decreases in cell number after lipid antigen stimulation, although they express equivalent TCR levels. In summary, the data presented here demonstrate that α-GalCer–specific NK T cells undergo a unique and highly compartmentalized response to antigenic stimulation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers

Matsuda

Naidenko

Gapin

et al. 2000

The Journal of Experimental Medicine

814

823

View full text Add to dashboard Cite

show abstract

“…These cells have been shown to suppress T‐cell‐dependent B‐cell responses in a H‐2 Qa‐1‐dependent manner and play an important role in maintenance of self‐tolerance 252. Qa‐1 and its human homolog HLA‐E are non‐classical MHC class Ib molecules that predominantly present a peptide derived from the signal sequence of classical MHC class Ia molecules, recognition of which by the inhibitory NK cell receptor NKG2A/CD94 contributes to inhibition of triggering of NK cell effector activity on contact with cells that express normal levels of MHC 1a molecules 253. However, MHC‐E can also present some peptides derived from autoantigens and pathogens, which are recognized by CD8 + T cells.…”

Section: Regulatory Cell Populations and Their Relationship To Bnab Imentioning

confidence: 99%

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Borrow

Moody

2017

Immunological Reviews

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SummaryInduction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse variants of human immunodeficiency virus type 1 (HIV‐1) is a key, as‐yet‐unachieved goal of prophylactic HIV‐1 vaccine strategies. However, some HIV‐infected individuals develop bnAbs after approximately 2‐4 years of infection, enabling analysis of features of these antibodies and the immunological environment that enables their induction. Distinct subsets of CD4+ T cells play opposing roles in the regulation of humoral responses: T follicular helper (Tfh) cells support germinal center formation and provide help for affinity maturation and the development of memory B cells and plasma cells, while regulatory CD4+ (Treg) cells including T follicular regulatory (Tfr) cells inhibit the germinal center reaction to limit autoantibody production. BnAbs exhibit high somatic mutation frequencies, long third heavy‐chain complementarity determining regions, and/or autoreactivity, suggesting that bnAb generation is likely to be highly dependent on the activity of CD4+ Tfh cells, and may be constrained by host tolerance controls. This review discusses what is known about the immunological environment during HIV‐1 infection, in particular alterations in CD4+ Tfh, Treg, and Tfr populations and autoantibody generation, and how this is related to bnAb development, and considers the implications for HIV‐1 vaccine design.

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“…Certain KIRs and Ly49 proteins recognize MHC class I molecules. Other NK-cell receptors recognize a broad range of stress-induced molecules and other non-classical MHC molecules 63,64 , as well as viral gene products 65,66 and other NK-cell receptors 67 . NK-cell activity has a broad phylogenetic distribution extending to invertebrates 68 .…”

Section: Nk and Nk-type Receptors In Jawed Vertebratesmentioning

confidence: 99%

Reconstructing immune phylogeny: new perspectives

2005

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Numerous studies of the mammalian immune system have begun to uncover profound interrelationships, as well as fundamental differences, between the adaptive and innate systems of immune recognition. Coincident with these investigations, the increasing experimental accessibility of non-mammalian jawed vertebrates, jawless vertebrates, protochordates and invertebrates has provided intriguing new information regarding the likely patterns of emergence of immune-related molecules during metazoan phylogeny, as well as the evolution of alternative mechanisms for receptor diversification. Such findings blur traditional distinctions between adaptive and innate immunity and emphasize that, throughout evolution, the immune system has used a remarkably extensive variety of solutions to meet fundamentally similar requirements for host protection.The evolutionary development of the METAZOANS was associated with the diversification of a wide range of specialized cell-surface molecules that mediate key metabolic processes, as well as provide crucial contact interfaces and carry out a broad range of other essential functions. It is not unexpected that some of these molecules also came to function as barriers to pathogenic invasion and, in doing so, began to carry out dedicated innate immune protective functions. Whereas the simplest form of protection, barrier formation, is essentially mechanical in nature, relentless pressure from genetic variation in pathogens probably drove the evolution of such innate immune protective molecules towards diversification and, in parallel, towards integration of signalling pathways to regulate cellular responses to external stimulation. However, despite the sophistication that such innate immune mediators achieved over time, their biological complexity, by definition, would be limited by genome space, so with increasing complexity of body plan and/or increasing pathogen sophistication, they could be overwhelmed. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMore than 500 million years ago, a TRANSPOSITION event, probably involving a recombinationactivating gene (RAG)-bearing element, might have given rise to the predecessors of the rearranging antigen-binding receptors of the jawed vertebrates, which encompass the vertebrate radiations that extend from the cartilaginous fish through to humans. This is considered the defining point in the emergence of RAG-mediated (conventional) adaptive immunity 1,2 , which has evolved to create a mechanism for deriving almost limitless variation from very few genes. Studies in traditional and non-traditional animal models, such as sharks, bony fish and birds, have brought this event and its ramifications for host defence into sharper focus. We can now predict much about how these rearranging antigenbinding receptors probably arose, what alternative pathways of immune-receptor gene evolution have occurred, what relationships exist between B-and T-cell-mediated immunity and natural killer (NK)-cell function, how complex immune ...

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HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C

Cited by 1,981 publications

References 25 publications

Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers

Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Reconstructing immune phylogeny: new perspectives

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