Why peptides? Their possible role in the evolution of MHC-restricted T-cell recognition

Nagy, Zoltán Á.; Lehmann, Paul; Falcioni, F.; Müller, Simone; Adorini, Luciano

doi:10.1016/0167-5699(89)90247-8

Cited by 50 publications

(23 citation statements)

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“…Self-reactive T cells are controlled either by their elimination in the thymus or by the induction of tolerance in the periphery (1,2). Both mechanisms depend on the ability of APCs to process and present self-peptides in the context of MHC molecules, although it is now apparent that not all possible peptides from a self-antigen are presented (3,4). These limitations in processing suggest that T cells specific for some determinants on self-proteins may escape tolerance and therefore be a part of the normal repertoire of T cells.…”

mentioning

confidence: 99%

The inability to process a self-peptide allows autoreactive T cells to escape tolerance.

Mamula

1993

The Journal of Experimental Medicine

117

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SummaryIt is now clear that antigen presenting cells (APCs) do not present all the possible peptides of self-proteins to the immune system. What then, is the fate oft cells specific for those self-peptides that escape processing? In this study, the COOH-terminal peptide (residues 81-104) of self cytochrome c (cyt c) elicited strong autoimmune T cells, as well as autoantibodies specific for this immunogen. These T cells did not respond to stimulation with the whole self cyt c molecule, demonstrating that APCs cannot process and present the self 81-104 peptide. Whereas mice were unresponsive to immunization with the whole mouse cyt c molecule, the mouse 81-104 fragment together with the whole self-molecule induced and amplified the autoimmune T cell response to sites within the 1-80 peptide. T cells that never contact the relevant self-peptide are functionally ignorant. They do not become tolerized or deleted, nor do they normally participate in immune responses to the native whole self-protein, since APCs cannot present the 81-104 peptide.

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confidence: 99%

The inability to process a self-peptide allows autoreactive T cells to escape tolerance.

Mamula

1993

The Journal of Experimental Medicine

117

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“…This structure evidently binds peptides derived from proteins either endogenously synthesized (for MHC class I) or exogenously acquired (for MHC class II) (4). T-cell receptors either recognize peptides and MHC molecules simultaneously or the peptide alone in "the context" of the MHC molecules (5,6).…”

mentioning

confidence: 99%

Evolution of the major histocompatibility complex: molecular cloning of major histocompatibility complex class I from the amphibian Xenopus.

Flajnik

Canel

Kramer

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Class I major histocompatibility complex (MHC) cDNA clones have been isolated from an expression library derived from mRNA of an MHC homozygous Xenopus laevis. The nucleotide and predicted amino acid sequences show definite similarity to MHC class I molecules of higher vertebrates. The immunoglobulin-like a-3 domain is more similar to the immunoglobulin-like domains of mammalian class II (3 chains than to those of mammalian class I molecules, and a tree based on nucleotide sequences of representative MHC genes is presented.

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“…self versus infectious agent versus nutriment [36]. Finally, recent findings demonstrating that similar but not identical peptide analogs of self-epitopes do not only interfere with T cell recognition, but even actively inhibit T cell responses suggest that also partially homolo gous peptides may play an important role in this type of control [37,38]. In such a scenario, the identification of hsp-reactive T cells within autoimmune lesions need not necessarily reflect their functioning as effectors of de struction.…”

Section: Concluding Remarks and Outlookmentioning

confidence: 99%

“…Therefore, the probability for MHC presentation of the shared hsp epitope derived from an exogenous or an endogenous source, respectively, may differ. Second, it has been shown that peptide homologous with minor ami no acid exchanges may bind to the MHC better than the natural eptiope [37], Evidence has even been presented that hsp peptides which differ in one or two amino acid positions from the nominal cognates actively interfere with the immune response to the nominal antigen [38]. Thus, the high but not necessarily full sequence similarity between hsp peptides derived from self, infectious agents or nutriment may crucially influence the final outcome of the anti-hsp response.…”

Section: Cross-reactive Hsp Peptides As Physiological Ingredients Of mentioning

confidence: 99%

Heat Shock Proteins and Autoimmunity: A Critical Appraisal

Kaufmann¹

1994

Int Arch Allergy Immunol

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Various lines of evidence suggest a close relationship between heat shock proteins (hsp) and numerous autoimmune diseases. However, the common interpretation of hsp as antigens which provide a direct link between infection and autoimmunity appears insufficient. Rather, anti-hsp immune responses seem to represent physiological constituents of immune homeostasis. hsp are found in different sources, including infectious agents, nutriment and self, and the development of autoimmune disease seems to be related to an unbalanced presentation of hsp peptides to the immune system from these different sources.

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Why peptides? Their possible role in the evolution of MHC-restricted T-cell recognition

Cited by 50 publications

References 50 publications

The inability to process a self-peptide allows autoreactive T cells to escape tolerance.

The inability to process a self-peptide allows autoreactive T cells to escape tolerance.

Evolution of the major histocompatibility complex: molecular cloning of major histocompatibility complex class I from the amphibian Xenopus.

Heat Shock Proteins and Autoimmunity: A Critical Appraisal

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