Design of high-affinity major histocompatibility complex-specific antagonist peptides that inhibit cytotoxic T-lymphocyte activity: implications for control of viral disease.
Cytotoxic T lymphocytes (CTLs) recognize viral antigens presented by infected cells in the context of their major histocompatibility complex glycoproteins. The irreversible killing of virus-infected cells by virus-specific CTLs can be the cause of serious disease, particularly in the central nervous, hepatic, and cardiovascular systems. Design of molecules controlling (blocking) interaction between CTLs and infected cells, and their further use to inhibit (or antagonize) T-lymphocyte activity, is an important pharmacologic goal. In this report, we describe the design of a new family of peptides which selectively inhibit activity of lymphocytic choriomeningitis virus-specific CD8+ T lymphocytes, which recognize endogenously processed viral epitopes presented by major histocompatibility complex class I molecules.
Gairin
J E
JE
Laboratoire de Pharmacologie et de Toxicologie Fondamentales, Centre National de la Recherche Scientifique, Toulouse, France.
Oldstone
M B
MB
D000409:Alanine / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001216:Asparagine / Q000276:immunology; D002460:Cell Line; D002860:Chromium Radioisotopes; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000276:immunology; D015195:Drug Design; D000939:Epitopes / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000187:drug effects*; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D014777:Virus Diseases / Q000188:drug therapy / Q000276:immunology
D000956:Antigens, Viral; D002860:Chromium Radioisotopes; D000939:Epitopes; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D010446:Peptide Fragments; D001216:Asparagine; D000409:Alanine