Major histocompatibility complex-based suppression: a mechanism for T-cell control

Gray, David W.

doi:10.1016/s0306-9877(98)90001-9

Cited by 7 publications

(3 citation statements)

References 55 publications

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“…The challenge now is to understand completely the mechanisms of this regulation with a view to designing induction strategies that deliver stable allograft tolerance in humans. As a footnote to these observations, it is interesting that recently it has been suggested that a normal and essential function of self MHC antigens in situations of noninflammation is to provide signals that prevent spontaneous T-cell proliferation (30). Experiments that test this model are difficult to design, but the results of the current study showing that exposure to allo-MHC without immunotherapy can generate regulatory T cells are not inconsistent with this hypothesis.…”

Section: "Random" Blood Transfusion Combined With Immunomodulation Gementioning

confidence: 53%

Pretransplant blood transfusion without additional immunotherapy generates CD25+CD4+ regulatory T cells: a potential explanation for the blood-transfusion effect

Bushell

Karim

Kingsley³

et al. 2003

Transplantation

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Section: "Random" Blood Transfusion Combined With Immunomodulation Gementioning

confidence: 53%

Pretransplant blood transfusion without additional immunotherapy generates CD25+CD4+ regulatory T cells: a potential explanation for the blood-transfusion effect

Bushell

Karim

Kingsley³

et al. 2003

Transplantation

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“…The exact molecular mechanism by which T‐cells are switched off remains uncertain. Some of the suggested mechanisms21–27 are listed in Table 2. What is becoming certain is that the mechanism involves cell‐cell contact and is, therefore, likely to be prevented by insertion of a membrane.…”

Section: Points Related To Islet Transplantation and Encapsulationmentioning

confidence: 99%

An Overview of the Immune System with Specific Reference to Membrane Encapsulation and Islet Transplantation

Gray

2001

Annals of the New York Academy of Sciences

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The concept of immunoisolation by use of a bioartificial membrane is discussed, concentrating on the immunological mechanisms that are likely to be operative in the light of recent information on the workings of the immune system. Special attention is given to the use of encapsulation for the purpose of treating autoimmune diabetes by implantation of xenogeneic islet tissue. It is argued that the term immunoisolation is misleading because the immune system is always activated by the indirect pathway of antigen presentation and that the term immunomodulation would be more appropriate.

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“…It was pointed out nearly 10 years ago [29] that, if one tried to produce a biological system for preventing HLA matching between individuals, it would be difficult to develop anything more effective than the HLA gene complex;. So maybe that is exactly what it is doing -not, one assumes, to prevent organ transplantation, but to protect some crucial function from masquerade, presumably by invading organisms.…”

Section: Development Of the Mhc-based Suppres-sion Hypothesismentioning

confidence: 99%

The MHC-Based Suppression (MBS) Theory: Implications for Transplantation

Gray¹

2008

TOTRANSJ

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Abstract:Complex areas of scientific endeavor may sometimes benefit from a theoretical and/or reductionist approach to guide the direction of future experiments, perhaps best illustrated by the field of cosmology. The field of immunology in general, and transplantation immunology in particular, is certainly complex. This commentary draws attention to a theory that proposes an alternative role for MHC molecules, placing them central to the process of tolerance induction, with major implications for transplantation and all fields of immunology.Key Words: Immune tolerance, MHC-based suppression, peptide/MHC complex, peripheral tolerance, regulatory T cells, xenotransplantation. WHAT IS KNOWN ABOUT MHC MOLECULES?Originally named as human leukocyte antigens (HLA), later the term major histocompatibility (MHC) antigens came into common use. In this article, the term HLA will be used to indicate the human system, whilst the term MHC will be used only to indicate a deliberate widening to include other mammalian species, all of which have a superficially similar immune system. Many of the immunological mechanisms and concepts mentioned are arguably established facts and will not be referenced, unless the point being made is of particular importance for the concepts presented here. The term "cognate ligand " is used to mean the combination of MHC and bound peptide which binds fully to a particular T cell receptor. HLA -THE HUMAN MHCHLA molecules have been under intensive investigation for more than 25 years and a number of remarkable features have been discovered. Firstly, there are several molecular families -HLA-A, HLA-B, HLA-C, HLA-DP, HLA-DQ, HLA-DR, HLA-E, HLA-F, HLA-G, HLA-H -that are structurally related (Ig superfamily) membrane-bound molecules with 4 immunoglobulin-like domains, an anchoring transmembrane portion, and a groove on the exterior portion of the molecule which normally has a peptide bound to it. (Further discussion will be limited to the "classical" HLA genes and their products, whereas HLA-E, HLA-F, HLA-G, HLA-H, will not be discussed further here). HLA-A, HLA-B and HLA-C form a more closely-related sub-group, called HLA Class 1, that use a constant molecule, 2 microglobulin, as one of the four domains. HLA-DP, HLA-DQ, HLA-DR form a second structurally-related subgroup, known as MHC Class *Address correspondence to this author at the Nuffield Department of Surgery, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK; Tel: 44(0)1865220145; Fax: 44(0)1865768876; E-mail: derek.gray@nds.ox.ac.uk II, that use two different double-Ig-like molecules to produce the 4-domain structure.Secondly, both MHC Class I and MHC Class II molecules exhibit genetically-coded (and therefore heritable) polymorphism that is so extensive that completely identical matching by non-related persons is rarely possible. Despite the polymorphism, all Type 1 and Type II MHC molecules are able to bind peptides derived from a wide range of proteins, holding them in the groove on the surface of the molecule, where they may be prese...

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Major histocompatibility complex-based suppression: a mechanism for T-cell control

Cited by 7 publications

References 55 publications

Pretransplant blood transfusion without additional immunotherapy generates CD25+CD4+ regulatory T cells: a potential explanation for the blood-transfusion effect

Pretransplant blood transfusion without additional immunotherapy generates CD25+CD4+ regulatory T cells: a potential explanation for the blood-transfusion effect

An Overview of the Immune System with Specific Reference to Membrane Encapsulation and Islet Transplantation

The MHC-Based Suppression (MBS) Theory: Implications for Transplantation

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