Immunization of mice with human immunodeficiency virus glycoprotein gp160 peptide 315-329 induces both class I- and class II-restricted T cells: not all T cells can respond to whole molecule stimulation.
The V3 loop of human immunodeficiency virus (HIV) glycoprotein gp160 is of interest as a possible site for protective immune responses. This article examines the murine T cell response to peptide 315-329 derived from HIV gp160. Surprisingly, immunization with peptide in complete Freund's adjuvant induced class I-restricted T cells as well as class II-restricted T cells. These data suggest that this peptide may have the unusual ability to enter the class I antigen processing pathway. Strategies that employ V3 loop peptides to induce protective immunity must generate T cells that can recognize epitopes derived from whole molecules in vivo. Therefore, peptide-induced T cells were tested for their ability to respond to naturally processed forms of gp120 and gp160 whole-molecule preparations. Peptide induced class I-restricted cells were capable of recognizing transfectants expressing gp160. However, only one of two class II-restricted T cell lines was capable of recognizing soluble whole molecules. This indicates that peptide immunization induces T cells that recognize a class II-restricted determinant that is not generated during normal processing of whole molecules. We have also examined the response of peptide primed T cells to lipidated peptide antigens. Lipidated peptides are generally considered to have increased antigenicity and immunogenicity as compared to normal peptides. However, lipidation of peptide 315-329 damaged both the class I- and II-restricted determinants, indicating that lipidation is not always desirable. The data presented here highlight a potential serious problem in the use of peptide vaccines, in that peptide immunization may not always induce T cells that can protect against a viral challenge.
Moore
R L
RL
Department of Microbiology and Immunology, University of Maryland, Baltimore 21201.
Fox
B S
BS
D000818:Animals; D002460:Cell Line; D000939:Epitopes; D015686:Gene Products, env / Q000276:immunology*; D006678:HIV / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D019302:HIV Envelope Protein gp160; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D011498:Protein Precursors / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D015686:Gene Products, env; D015488:HIV Antigens; D019302:HIV Envelope Protein gp160; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010169:Palmitic Acids; D010446:Peptide Fragments; D011498:Protein Precursors; D019308:Palmitic Acid