Deletion of CD4 and CD8 coreceptors permits generation of alphabetaT cells that recognize antigens independently of the MHC.

TitleDeletion of CD4 and CD8 coreceptors permits generation of alphabetaT cells that recognize antigens independently of the MHC.
Publication TypeJournal Article
Year of Publication2007
AuthorsVan Laethem F, Sarafova SD, Park J-H, Tai X, Pobezinsky L, Guinter TI, Adoro S, Adams A, Sharrow SO, Feigenbaum L, Singer A
JournalImmunity
Volume27
Issue5
Pagination735-50
Date Published2007 Nov
ISSN1074-7613
KeywordsAnimals, Antigens, CD4, Antigens, CD8, Blotting, Northern, Cell Differentiation, Flow Cytometry, Fluorescent Antibody Technique, Immunoprecipitation, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Major Histocompatibility Complex, Mice, Mice, Transgenic, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Thymus Gland
Abstract

The thymus generates major histocompatibility complex (MHC)-restricted alphabetaT cells that only recognize antigenic ligands in association with MHC or MHC-like molecules. We hypothesized that MHC specificity might be imposed on a broader alphabetaTCR repertoire during thymic selection by CD4 and CD8 coreceptors that bind and effectively sequester the tyrosine kinase Lck, thereby preventing T cell receptor (TCR) signaling by non-MHC ligands that do not engage either coreceptor. This hypothesis predicts that, in coreceptor-deficient mice, alphabeta thymocytes would be signaled by non-MHC ligands to differentiate into alphabetaT cells lacking MHC specificity. We now report that MHC-independent alphabetaT cells were indeed generated in mice deficient in both coreceptors as well as MHC (“quad-deficient” mice) and that such mice contained a diverse alphabetaT cell repertoire whose MHC independence was confirmed at the clonal level. We conclude that CD4 and CD8 coreceptors impose MHC specificity on a broader alphabetaTCR repertoire during thymic selection by preventing thymocytes from being signaled by non-MHC ligands.

DOI10.1016/j.immuni.2007.10.007
Alternate JournalImmunity
PubMed ID18023370