Genomics-based identification of self-ligands with T cell receptor-specific biological activity.
Self-peptide/major histocompatibility complex (MHC) complexes profoundly influence the biology of T lymphocytes. They promote the selection of the T cell receptor (TCR) repertoire in the thymus, maintain the homeostasis of peripheral T cells prior to encounter with antigen, and modify the responsiveness of T cells to foreign antigens. In addition, they can serve as antigens for autoaggressive T cells that induce autoimmune diseases. The complete sequencing of the genomes of human, mouse, and many pathogenic organisms now provides us with a comprehensive list of all possible proteins that may be the source of foreign antigenic and self-peptides. A computational approach using profile-based similarity searches on potential self-MHC-binding peptides can be used to efficiently predict self-peptides with biological activities. The common feature of the identified peptides is similarity to antigen. Thus, self-peptides may form 'hazy' images of the universe of antigens that are used as templates to create and maintain the TCR repertoire.
Santori
Fabio R
FR
Michael Heidelberger Division of Immunology, Department of Pathology and NYU Cancer Center, New York, NY 10016, USA.
Brown
Stuart M
SM
Vukmanović
Stanislav
S
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000235:genetics*; D015551:Autoimmunity; D002454:Cell Differentiation; D023281:Genomics; D006183:H-2 Antigens / Q000235:genetics; D006801:Humans; D008285:Major Histocompatibility Complex; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018716:Molecular Mimicry; D010047:Ovalbumin / Q000276:immunology; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D001324:Autoantigens; D006183:H-2 Antigens; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin