Peptide-mediated immunosuppression

Current Opinion in Immunology

Volumn 9, Issue 5, 1997, Pages 669-675

  Magee, Colm C ^a   Sayegh, Mohamed H ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; T LYMPHOCYTE RECEPTOR;

ALLOIMMUNITY; ANTIGEN PRESENTING CELL; IMMUNOMODULATION; IMMUNOSUPPRESSIVE TREATMENT; REVIEW;

EID: 0030711051     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0952-7915(97)80047-7     Document Type: Article

References (59)

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26. + T lymphocytes in vitro and in vivo. of outstanding interest J Immunol. 157:1996;87-100 Peptides corresponding to the CD4 binding regions of murine MHC class II molecules modulated in vitro CD4-dependent immune responses against alloantigen and superantigen: low doses stimulated and high doses inhibited lymphocyte proliferation. Although antigen specific T lymphocyte responses in vivo were actually enhanced by the systemic administration of the peptides, targeting and disrupting CD4 - MHC class II interactions is a promising area of immunomodulatory therapy.
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45. u. Possible mechanisms of action of allochimeric proteins are discussed.
46. MacDonald CM, Bolton EM, Jaques BC, Walker KG, Bradley JA. Reduction of alloantibody response to class I major histocompatibility complex by targeting synthetic allopeptides for presentation by B cells. of special interest Transplantation. 63:1997;926-932 An interesting mechanism of targeting and inactivating T cells specific for immunodominant peptides by presenting these peptides via resting (non costimulating) B cells. Although allograft survival was not prolonged, T helper cell assisted alloantibody production was reduced.
47. Liu Z, Colovai AI, Tugulea S, Reed EF, Fisher PE, Mancini D, Rose EA, Cortesini R, Michler RE, Suciu-Foca N. Indirect recognition of donor HLA-DR peptides in organ allograft rejection. of outstanding interest J Clin Invest. 98:1996;1150-1157 An important study demonstrating the role of indirect recognition in human cardiac allograft rejection. T cell reactivity to certain donor allopeptides was found to correlate with episodes of acute graft rejection. Of the 32 studied cardiac transplant recipients, 19 were mismatched for two HLA-DR antigens. In the majority of these patients, absence of acute graft rejection was associated with absence of indirect alloreactivity against immunodominant peptides derived from the mismatched donor HLA-DR molecules. In contrast, acute rejection episodes were usually associated with evidence of indirect alloreactivity (restricted by one recipient HLA-DR molecule) against an immunodominant peptide of only one donor HLA molecule. In patients with multiple rejection episodes, however, alloreactivity developed against the second donor HLA-DR molecule. This phenomenon of intermolecular spreading strongly suggests that the early modulation of indirect alloresponses will be much more effective in limiting graft rejection.
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51. *0101 were tested for their ability to modulate T cell responses to the wild-type peptide antigen. Two of these analogues inhibited such responses by TCR antagonism; two others acted as TCR agonists but induced high zone tolerance at higher concentrations in vitro.
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54. + T cells alone, rather than unpurified T cells. Donor lymphocytes harvested from the thoracic duct exhibited a specific reduction in alloreactivity (as measured by the mixed lymphocyte reaction) to host splenocytes.
55. Koch U, Korngold R. A synthetic CD4-CDR3 peptide analog enhances bone marrow engraftment across major histocompatibility barriers. of special interest Blood. 89:1997;2880-2890 The rD-mPGPtide peptide improved allogeneic bone marrow engraftment (assessed by donor-host chimerism) in three different mouse strain combinations. Peptide treated mice in the haploidentical and MHC class II mismatched strain combinations demonstrated tolerance to both donor- and matched strain combinations demonstrated tolerance to both donor- and syngeneic host-type skin grafts but still rejected third party grafts.
56. + T cell inhibition.
57. + T cell mediated rejection and autoimmune diseases.
58. Satoh T, Aramini JM, Li S, Friedman TM, Gao J, Edling AE, Townsend R, Koch U, Choski S, Germann MW, et al. Bioactive peptide design based on protein surface epitopes. A cyclic heptapeptide mimics CD4 domain 1 CC' loop.and inhibits CD4 biological function. of outstanding interest J Biol Chem. 272:1997;12175-12180 Computer analysis of CD4 domain 1 revealed a potential MHC class II molecule binding pocket, formed in part by a protruding CC' loop. Analogue peptides of this loop were tested for inhibition of the human CD4-MHC class II interaction. A small cyclic peptide was the most potent analogue in vitro and nuclear magnetic resonance spectroscopy showed that it closely mimicked the loop's structure. Modification of skin allograft rejection and experimental allergic encephalomyelitis by this cyclic peptide was demonstrated in murine models. Thus, identification and disruption of small peptide regions critical for protein - protein interactions are useful tools for designing new immunomodulatory agents.
59. Li S, Gao J, Satoh T, Friedman TM, Edling AE, Koch U, Choksi S, Han X, Korngold R, Huang Z. A computer screening approach to immunoglobulin superfamily structures and interactions: discovery of small non-peptidic CD4 inhibitors as novel immunotherapeutics. of outstanding interest Proc Natl Acad Sci USA. 94:1997;73-78 A computer screening method was used to identify nonpeptide organic ligands of the CD4 domain binding pocket discussed above [58]. Three such compounds inhibited T cell proliferation in the human mixed lymphocyte reaction assay and demonstrated immunoinhibitory effects in experimental allergic encephalomyelitis and skin allograft models. The implications of this computer screening approach are discussed.