The half-life of the T-cell receptor/peptide-major histocompatibility complex interaction can modulate T-cell activation in response to bacterial challenge

被引:25
作者
Carreno, Leandro J.
Bueno, Susan M.
Bull, Paulina
Nathenson, Stanley G.
Kalergis, Alexis M.
机构
[1] Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept Mol Genet & Microbiol, Santiago, Chile
[2] Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept Reumatol, Santiago, Chile
[3] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA
[4] Millennium Nucleus Immunol & Immunotherapy, Santiago, Chile
关键词
dendritic cells; major histocompatibility complex; T cells; T-cell receptors;
D O I
10.1111/j.1365-2567.2007.02561.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
T-cell activation results from engagement of the T-cell receptor (TCR) by cognate peptide-major histocompatibility complex (pMHC) complexes on the surface of antigen-presenting cells (APC). Previous studies have provided evidence supporting the notion that the half-life of the TCR/pMHC interaction and the density of pMHC on the APC are two parameters that can influence T-cell activation. However, whether the half-life of the TCR/pMHC interaction can modulate T-cell activation in response to a pathogen challenge remains unknown. To approach this question, we generated strains of bacteria expressing variants of the ovalbumin (OVA) antigen, carrying point mutations in the SIINFEKL sequence. When bound to H-2K(b), this peptide is the cognate ligand for the OT-I TCR. Variants of the H-2K(b)/SIINFEKL bind to the OT-I TCR with distinct half-lives. Here we show that dendritic cells (DCs) infected with bacteria expressing OVA variants were incapable of activating OT-I T cells when the half-life of the TCR/H-2K(b)/OVA interaction was excessively short. Consistent with these data, T-cell activation was only observed in mice infected with bacteria expressing OVA variants that bound to OT-I with a half-life above a certain threshold. Considered together, our data suggest that the half-life of TCR/pMHC interaction can significantly modulate T-cell activation in vivo, as well as influence recognition of antigens expressed by bacteria. These observations underscore the importance of the TCR/pMHC half-life on the clearance of pathogens.
引用
收藏
页码:227 / 237
页数:11
相关论文
共 58 条
[51]   Serial triggering of TCRs: A basis for the sensitivity and specificity of antigen recognition [J].
Valitutti, S ;
Lanzavecchia, A .
IMMUNOLOGY TODAY, 1997, 18 (06) :299-304
[52]   SERIAL TRIGGERING OF MANY T-CELL RECEPTORS BY A FEW PEPTIDE-MHC COMPLEXES [J].
VALITUTTI, S ;
MULLER, S ;
CELLA, M ;
PADOVAN, E ;
LANZAVECCHIA, A .
NATURE, 1995, 375 (6527) :148-151
[53]   SUSTAINED SIGNALING LEADING TO T-CELL ACTIVATION RESULTS FROM PROLONGED T-CELL RECEPTOR OCCUPANCY - ROLE OF T-CELL ACTIN CYTOSKELETON [J].
VALITUTTI, S ;
DESSING, M ;
AKTORIES, K ;
GALLATI, H ;
LANZAVECCHIA, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 181 (02) :577-584
[54]   Salmonella inhibit T cell proliferation by a direct, contact-dependent immunosuppressive effect [J].
van der Velden, AWM ;
Copass, MK ;
Starnbach, MN .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (49) :17769-17774
[55]   Evidence for antibody-mediated enhancement of simian immunodeficiency virus (SIV) Gag antigen processing and cross presentation in SIV-infected rhesus macaques [J].
Villinger, F ;
Mayne, AE ;
Bostik, P ;
Mori, K ;
Jensen, PE ;
Ahmed, R ;
Ansari, AA .
JOURNAL OF VIROLOGY, 2003, 77 (01) :10-24
[56]   Costimulation and endogenous MHC ligands contribute to T cell recognition [J].
Wülfing, C ;
Sumen, C ;
Sjaastad, MD ;
Wu, LC ;
Dustin, ML ;
Davis, MM .
NATURE IMMUNOLOGY, 2002, 3 (01) :42-47
[57]   Antigen-presenting cells and anti-Salmonella immunity [J].
Yrlid, U ;
Svensson, M ;
Kirby, A ;
Wick, MJ .
MICROBES AND INFECTION, 2001, 3 (14-15) :1239-1248
[58]   Alloantigen affinity and CD4 help determine severity of graft-versus-host disease mediated by CD8 donor T cells [J].
Yu, Xue-Zhong ;
Albert, Michael H. ;
Anasetti, Claudio .
JOURNAL OF IMMUNOLOGY, 2006, 176 (06) :3383-3390