A structure-based approach to designing synthetic CD8alpha peptides that can inhibit cytotoxic T-lymphocyte responses.
CD8 molecules function as co-receptors on cytotoxic T lymphocytes (CTLs), interacting with a nonpolymorphic region of the major histocompatibility complex (MHC) class I a3 domain on antigen-presenting cells. Analogues were designed from a structural model of the mouse CD8a molecule to identify surfaces involved in CD8 function. Peptides were screened for in vitro biological activity on alloreactive CTLs, and analogue SC4 (p54-59) was found to be inhibitory during both the generation and effector stages. SC4 was also able to significantly prolong skin allograft survival across a MHC class I barrier. Thus, such CD8 analogues may have therapeutic potential as immunoregulators of CTL immune responses.
Choksi
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S
Kimmel Cancer Institute, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Jameson
B A
BA
Korngold
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R
D000818:Animals; D016827:CD8 Antigens / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects*; D006183:H-2 Antigens; D051379:Mice; D008958:Models, Molecular; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D016038:Skin Transplantation / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*; D014184:Transplantation, Homologous
D016827:CD8 Antigens; D006183:H-2 Antigens; D009842:Oligopeptides; D010446:Peptide Fragments