Endogenous altered peptide ligands can affect peripheral T cell responses. J Exp Med 1996 Apr 01;183(4):1311-21
Date
04/01/1996Pubmed ID
8666889Pubmed Central ID
PMC2192490DOI
10.1084/jem.183.4.1311Scopus ID
2-s2.0-0029862940 (requires institutional sign-in at Scopus site) 60 CitationsAbstract
T cells potentially encounter a large number of endogenous self-peptide/MHC ligands in the thymus and the periphery. These endogenous ligands are critical to both positive and negative selection in the thymus; however, their effect on peripheral T cells has not been directly ascertained. Using the murine allelic Hbd (64-76)/I-Ek self-antigen model, we have previously identified altered peptide ligands (APLs) which are able to stimulate some but not all TCR-mediated effector functions. To determine directly the effect of endogenously synthesized APL/MHC complexes on peripheral T cells, we used a TCR transgenic mouse which had reversed our normal antigen system, with Ser69 peptide now being the agonist and Hbd(64-76) being the APL. In this report, we show that the constitutive level of endogenous Hbd(64-76)/I-Ek complexes presented by APCs in vivo is too low to affect the response of Ser69 reactive T cells. However, by increasing the number of Hbd(64-76)/I-Ek complexes expressed by the APCs, TCR antagonism is observed for both primary T cells and T cell hybridomas. In addition, the level of the CD4 coreceptor expressed on T cells and T cell hybridomas. In addition, the level of the CD4 coreceptor expressed on T cells changes the response pattern to endogenously presented Hbd(64-76)/I-Ek ligand. These findings demonstrate that T cells are selected to ignore the constitutive levels of endogenous complexes they encounter in the periphery. T cell responses can be affected by endogenous APLs in the periphery under limited but attainable circumstances which change the efficacy of the TCR/ligand interaction. Thus, endogenous APLs play a role in both the selection of T cells in the thymus and the responses of peripheral T cells.
Author List
Vidal K, Hsu BL, Williams CB, Allen PMAuthor
Calvin B. Williams PhD, MD Chief, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntigen Presentation
Antigen-Presenting Cells
Base Sequence
CD4 Antigens
Cell Line
Hemoglobins
Histocompatibility Antigens
Ligands
Lymphocyte Activation
Mice
Mice, Transgenic
Molecular Sequence Data
Peptides
Receptors, Antigen, T-Cell, alpha-beta
T-Lymphocytes
