A synthetic dimeric HLA class I peptide inhibits T cell activity in vitro and prolongs allogeneic heart graft survival in a mouse model.
Transplantation
; 60(10): 1156-63, 1995 Nov 27.
Article
en En
| MEDLINE
| ID: mdl-7482725
ABSTRACT
A peptide derived from the alpha 1 domain of the human HLA class I heavy chain (amino acids 75-84; B2702.75-84) has been shown to inhibit human cytotoxic T and NK cell activity in a non-allele-restricted manner. In vivo, this peptide prolonged skin allograft survival in a murine model. Here we demonstrate prolongation of heart allograft survival in mice and extend the characterization of the immunomodulatory activity of B2702.75-84. Similar to what has been observed with retrovirus-derived peptides, the inhibitory capability of this peptide was increased when bound to a carrier protein. An increased immunomodulatory activity was also observed with the dimeric peptide B2702.84-75-75-84 or the multimeric B2702.75-84.MAP. This peptide not only inhibited cytotoxic T and NK cells but also anti-CD3-induced T cell proliferation as well as a mixed lymphocyte reaction (MLR). Flow cytometric analysis of T cells harvested from anti-CD3-stimulated spleen cell culture in the presence of B2702.84-75-75-84 showed decreased expression of activation markers (CD25, ICAM-1, Pgp-1, CD69) compared with untreated control cultures. The superior activity of B2702.84-75-75-84 could also be demonstrated in vivo. Administration of B2702.84-75-75-84 prolonged the survival of B6 (H2b) hearts in CBA (H2k) recipients to 15 +/- 2.7 (P = 0.0002 vs. control) days compared with 11.4 +/- 2.6 (P = 0.01) days in B2702.75-84 treated animals and 7.5 +/- 1.1 days in untreated controls. Administration of control peptides had no significant effect on allograft survival. In combination with a subtherapeutic dose of cyclosporine, B2702.75-84 induced long-term graft survival in 60% of recipients.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Linfocitos T
/
Antígenos de Histocompatibilidad Clase I
/
Trasplante de Corazón
/
Supervivencia de Injerto
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Transplantation
Año:
1995
Tipo del documento:
Article
País de afiliación:
Estados Unidos