During the past year, almost 600 peptides have been produced by the laboratory. Many have been used for defining MHC class I restricted T cell epitopes e.g. for influenza and myelin basic protein (multiple sclerosis), and for defining the nature of the interaction between class I molecules and peptides, to study mechanisms of antigen processing, to examine the specificity of natural killer (NK) cell receptors, and to map antibody epitopes. Peptides have also been used for preparing antisera to a large variety of proteins including integrins, NK receptors (NKG2), Fc receptors, virus proteins, human histamine I receptor, gag polypeptide of a neurovirulent murine retrovirus, human ZAP-70, purinergic receptor, RAG-2, thymidine kinase, OX-40, feline calicvirus protease, alpha-tubulin I, HIV-Rex, noval viral gene (VZV), and various oncogenes such as JUN and REL. Peptides have also been used to study the functional activity of HIV Tax and Rev proteins, malaria parasite invasion, Ras-related proteins in the activation of NADPH oxidase, B cell transcription factors, NK recognition, NF-kappa beta and I kappa beta, trafficking of malaria proteins, pathogenic scrapie-associated PrP, MuLV infection, vaccinia proteins, Kaposi sarcoma virus proteins, MAIDS viral proteins, HIV replication, and hepatitis E proteins. Peptides have also been used to study disease related T cell epitopes for rheumatoid arthritis, multiple sclerosis, experimental allergic encephalomyelitis (EAE), experimental myasthenia gravis, autoimmune gastritis and Schistosoma mansoni. The expression of class I major histocompatibility complex antigens on the surface of cells transformed by adenovirus 12 (Ad12) is generally very low, and correlates with the high oncogenicity of this virus. In primary embryonal fibroblasts from transgenic mice that express both endogenous H-2 genes and a miniature swine class I gene (PD1), Ad12- mediated transformation results in suppression of cell surface expression of all class I antigens. Although class I mRNA levels of PD1 and H-2Db are similar to those in nonvirally transformed cells, recognition of newly synthesized class I molecules by a panel of monoclonal antibodies is impaired, presumably as a result of inefficient assembly and transport of the class I molecules. Analysis of steady state mRNA levels of the TAP1 and TAP2 transporter genes for Ad12-transformed cell lines revealed that they both are significantly reduced. Reconstitution of PD1 and H- 2Db, but not H-2Kb, expression is achieved in an Ad12-transformed cell line by stable transfection with a TAP2, but not a TAP1, expression construct. From these data it may be concluded that suppressed expression of peptide transporter genes, especially TAP2, in Ad12- transformed cells inhibits cell surface expression of class I molecules. These results suggest that suppression of peptide transporter genes might be an important mechanism whereby virus-transformed cells escape immune recognition in vivo.
