Endogenous altered peptide ligands can affect peripheral T cell responses.
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.
Vidal
K
K
Center for Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Hsu
B L
BL
Williams
C B
CB
Allen
P M
PM
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells; D001483:Base Sequence; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D006454:Hemoglobins / Q000235:genetics / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D006454:Hemoglobins; D006649:Histocompatibility Antigens; D008024:Ligands; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta