Self/nonself discrimination among immunoregulatory (CD4) T cells

Mitchison, N. A.; Katz, David R.; Chain, Benjamin M.

doi:10.1006/smim.2000.0229

Cited by 6 publications

(5 citation statements)

References 42 publications

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“…Presentation of antigen by non-professional APCs residing in non-lymphoid organs was for long viewed as a major mechanism for peripheral T cell tolerance (34). The study presented in this report shows that exposure to tolerogen in vivo leads to contact between the target T cells and APCs rather in lymphoid tissues with minimal interactions in non-lymphoid organs such as the liver, lung or intestinal wall (Fig.…”

Section: Discussionmentioning

confidence: 99%

T Cell Dynamics during Induction of Tolerance and Suppression of Experimental Allergic Encephalomyelitis

Divekar

Haymaker

Cascio

et al. 2011

The Journal of Immunology

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The cell dynamics associated with induction of peripheral T cell tolerance remain largely undefined. Herein, an in vivo model was adapted to two-photon microscopy imaging and T cell behavior was analyzed upon tolerogen-induced modulation. Fcγ receptor-deficient (FcγR−/−) mice were unable to resist or ameliorate experimental allergic encephalomyelitis (EAE) when treated with Ig-MOG tolerogen, an Ig carrying the myelin oligodendrocyte glycoprotein (MOG) 35–55 peptide. However, when FcγR+/+ dendritic cells (DC) are adoptively transferred into FcγR−/− mice, uptake and presentation of Ig-MOG occurs and the animals were able to overcome EAE. We then fluorescently labeled FcγR+/+ DC and 2D2 MOG-specific TCR-transgenic T cells, transferred them into FcγR−/− mice, administered Ig-MOG and analyzed both T cell-DC contact events and T cell motility. The results indicate that tolerance takes place in lymphoid organs and surprisingly the T cells do not become anergic but instead have a Th2 phenotype. The tolerant Th2 cells displayed reduced motility after tolerogen exposure similar to Th1 cells following immunization. However, the Th2 cells had higher migration speeds and took longer to exhibit changes in motility. Therefore, both Th1 immunity and Th2 tolerance alter T cell migration upon antigen recognition, but the kinetics of this effect differ among the subsets.

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Section: Discussionmentioning

confidence: 99%

T Cell Dynamics during Induction of Tolerance and Suppression of Experimental Allergic Encephalomyelitis

Divekar

Haymaker

Cascio

et al. 2011

The Journal of Immunology

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“…The language of self and non‐self has its foundations in a metchnikovian image of competitive struggle between organisms and infectious agents ( e.g. , bacteria and viruses)34 and reflects the dichotomy between benign and toxic, protection and damage, internal and external 35, 36, 37. In this perspective, intentionality and teleology become the molecular biochemistry of the immune response.…”

Section: Discussionmentioning

confidence: 99%

Non‐self‐discrimination as a driving concept in the identification of an immunodominant HMW‐MAA epitopic peptide sequence by autoantibodies from melanoma cancer patients

Dummer

Mittelman

Fanizzi³

et al. 2004

Intl Journal of Cancer

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We analyzed the sera of patients with melanoma to define the human humoral autoantibody profile towards HMW-MAA. Computational proteome scanning using the non-selfdiscrimination principle as a guide led to the individuation of the low-similarity HMW-MAA 781 The vast majority of melanomas develop from cutaneous intraepidermal melanocytes either in normal skin or within melanocytic nevi and progress through radial and vertical growth phases. Cutaneous melanoma accounts for about 10% of skin cancer cases but 75% of skin cancer deaths. The incidence of cutaneous melanoma is rising steadily worldwide, and the median survival of patients with distant metastases remains Ͻ1 year. 1,2 Adolescent cases are on the rise too: the incidence of melanoma increased by 85% among 15-to 19-year-olds from 1973 to 1996. 3 This situation demands efforts to develop new biologic therapies. 4 A promising approach is the use of specific immunotherapy with peptide-based vaccine strategies. Conditio sine qua non to this goal is the identification of immunogenic tumor antigens, including antigenic peptides able to evoke humoral/cellular responses. [5][6][7] Melanoma presents a heterogeneous pattern of various tumor markers, including melanocytic antigens and cancer testis antigens. 8 Among them, HMW-MAA 9 is a melanoma marker of particular interest since (i) it is highly expressed at the surface of tumor cells, (ii) it has restricted distribution in normal tissues 10 -12 and (iii) the induction of specific humoral response to anti-idiotypic anti-HMW-MAA MAb increases survival in patients with advanced melanoma. 13,14 Given these premises, identification of the epitopic sequences of this proteoglycan MAA is of great interest for obtaining specific antibodies to activate the destruction of melanoma cells. However, the dimensions of the HMW-MAA molecule do not allow the definition of HMW-MAA conformational determinants and hamper the exact individuation of the immunogenic linear peptide portions of this antigen through the usual epitope mapping methodology.We have used computational biology to exploring TAA epitopes recognized by MAbs or polyclonal antibodies. [15][16][17][18] By measuring the antigenic peptide similarity to the host's proteome, we demonstrated that a low level of similarity is a necessary condition for a peptide to be immunogenic. Consequently, based on the assumption that antigenic motifs that are scarcely represented in human proteins may offer epitopic determinants unknown to the host, we searched for immunogenic epitopes of the human melanomaassociated chondroitin sulfate proteoglycan by, first, selecting for portions of the HMW-MAA not shared with the human proteome and, then, analyzing the low-similarity peptide reactivity pattern using sera from 26 melanoma patients.

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“…The notion of tolerance arose pari passu with adaptive immunity from the evidence that not all antigens induce an immune response, that antigens varied in their immunogenicity, and that in any case there was the problem of self / non-self discrimination. 109 Despite newer variations on the theme that have incorporated responses of a non-adaptive nature (the danger hypothesis 110 and the discovery of less-exquisitely selective innate immune receptors responding to foreign antigens 111 ), the ideas of tolerance and immunity to antigens form the basis of immunological dogma. Meanwhile, immune privilege has been viewed until recently as an interesting curiosity related to specific tissues or sites in the organism, which were exceptions or refinements proving the rules of the larger concepts of tolerance and immunity.…”

Section: Review Tolerance Vs Privilegementioning

confidence: 99%

Immune privilege or privileged immunity?

et al. 2008

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Immune privilege is a concept that has come of age. Where previously it was considered to be a passive phenomenon restricted to certain specialized tissues, it is now viewed as comprising several mechanisms, both active and passive, shared in many aspects with emerging notions of the mechanisms of peripheral tolerance. The relative degrees of immune privilege vary from tissue to tissue depending on the number and strength of each of the mechanisms contained in that tissue. Immune privilege can be generated in non-privileged sites such as the skin and allografts, and is a property of the tissue itself. We therefore propose that, in addition to canonical central and peripheral tolerance mechanisms, there is a third route whereby the organism promotes self-antigen non-reactivity centered on the specific properties of each tissue and varying accordingly (relative degrees of immune privilege). This third mechanism of inducing immunological tolerance, as it is a local tissue phenomenon, might have particular therapeutic significance, for instance in devising strategies for induction of immunity to tumors by disrupting immune privilege or in preventing graft rejection by promoting immune privilege.

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Self/nonself discrimination among immunoregulatory (CD4) T cells

Cited by 6 publications

References 42 publications

T Cell Dynamics during Induction of Tolerance and Suppression of Experimental Allergic Encephalomyelitis

T Cell Dynamics during Induction of Tolerance and Suppression of Experimental Allergic Encephalomyelitis

Non‐self‐discrimination as a driving concept in the identification of an immunodominant HMW‐MAA epitopic peptide sequence by autoantibodies from melanoma cancer patients

Immune privilege or privileged immunity?

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