Intrinsic CD4+ T cell sensitivity and response to a pathogen are set and sustained by avidity for thymic and peripheral complexes of self peptide and MHC.
Interactions of T cell antigen receptors (TCRs) with complexes of self peptide and major histocompatibility complex (MHC) are crucial to T cell development, but their role in peripheral T cell responses remains unclear. Specific and nonspecific stimulation of LLO56 and LLO118 T cells, which transgenically express a TCR specific for the same Listeria monocytogenes epitope, elicited distinct interleukin 2 (IL-2) and phosphorylated kinase Erk responses, the strength of which was set in the thymus and maintained in the periphery in proportion to the avidity of the binding of the TCR to the self peptide-MHC complex. Deprivation of self peptide-MHC substantially compromised the population expansion of LLO56 T cells in response to L. monocytogenes in vivo. Despite their very different self-reactivity, LLO56 T cells and LLO118 T cells bound cognate peptide-MHC with an identical affinity, which challenges associations made between these parameters. Our findings highlight a crucial role for selecting ligands encountered during thymic 'education' in determining the intrinsic functionality of CD4+ T cells.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Stephen P
SP
Persaud
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Chelsea R
CR
Parker
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Wan-Lin
WL
Lo
Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, USA.
K Scott
KS
Weber
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Paul M
PM
Allen
D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D020349:Surface Plasmon Resonance; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014162:Transfection
D001324:Autoantigens; D011948:Receptors, Antigen, T-Cell