Epitopes described in "Natural and synthetic non-peptide antigens recognized by human gamma delta T cells."

Reference
Article Authors:Y Tanaka; C T Morita; Y Tanaka; E Nieves; M B Brenner; B R Bloom
Article Title:Natural and synthetic non-peptide antigens recognized by human gamma delta T cells.
Reference Detail
Reference ID:1000562
Abstract:T lymphocytes express either alpha beta or gamma delta T-cell receptor heterodimers. Most alpha beta T cells recognize antigenic peptides bound to major histocompatibility complex molecules but the antigen recognition and biological function of gamma delta T cells is unknown. A major human gamma delta T-cell subset expressing V gamma 2 and V delta 2 germline genes, but having diverse junctional sequences, is found in human mycobacterial lesions and responds in vitro to antigens of bacteria and parasites. In addition, certain haematopoietic tumour cells are specifically recognized and lysed by these T cells. V gamma 2V delta 2-bearing T cells were shown to recognize mycobacterial antigens that are protease resistant and phosphatase sensitive. Because of the difficulty in isolating natural antigens from mycobacterial culture filtrates or extracts, we synthesized a series of monoalkyl phosphates, and found that some, particularly monoethyl phosphate, could mimic the activity of mycobacterial antigens in stimulating these gamma delta T cells. Here we report the identification of natural antigens produced by mycobacteria recognized by human V gamma 2V delta 2-bearing T cells as isopentenyl pyrophosphate and related prenyl pyrophosphate derivatives, compounds involved in the synthesis of complex polyisoprenoid compounds in microbial and mammalian cells. Substitution of phosphate for the pyrophosphate moiety, or elimination of the double bond, greatly reduced antigenic activity of these compounds. These results provide formal evidence that, in contrast to recognition of major histocompatibility complex-bound peptide antigens by alpha beta T cells, human gamma delta T cells can recognize naturally occurring small non-peptidic antigens.
Affiliations:Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Date:1995
Reference Type:Literature
PubMed ID:7753173
Journal:Nature
Journal Volume:375
Article Pages:155-8
Journal ISSN:1476-4687
Article Chemical List:Antigens, Bacterial;Diphosphates;Hemiterpenes;Organophosphorus Compounds;Receptors, Antigen, T-Cell, gamma-delta;isopentenyl pyrophosphate
Article MeSH List:Antigens, Bacterial(immunology); Cell Line; Clone Cells; Diphosphates(chemistry; immunology); Hemiterpenes; Humans; Mycobacterium(immunology); Mycobacterium tuberculosis(immunology); Organophosphorus Compounds(immunology); Receptors, Antigen, T-Cell, gamma-delta(immunology); T-Lymphocytes(immunology)
Curation Last Updated:2014-09-11 20:01:54