Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis

被引:35
作者
Appel, H
Kuon, W
Kuhne, M
Wu, PH
Kuhlmann, S
Kollnberger, S
Thiel, A
Bowness, P
Sieper, J
机构
[1] Charite, Dept Gastroenterol Infectiol & Rheumatol, Berlin, Germany
[2] Deutsch Rheumaforschungszentrum Berlin, Berlin, Germany
[3] John Radcliffe Hosp, Inst Mol Med, MRC HIU, Oxford OX3 9DU, England
关键词
HLA-B27; T cells; tetramers; reactive arthritis;
D O I
10.1186/ar1221
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Reports of the use of HLA-B27/peptide tetrameric complexes to study peptide-specific CD8(+) T cells in HLA-B27(+)-related diseases are rare. To establish HLA-B27 tetramers we first compared the function of HLA-B27 tetramers with HLA-A2 tetramers by using viral epitopes. HLA-B27 and HLA-A2 tetramers loaded with immunodominant peptides from Epstein Barr virus were generated with comparable yields and both molecules detected antigen-specific CD8(+) T cells. The application of HLA-B27 tetramers in HLA-B27-related diseases was performed with nine recently described Chlamydia-derived peptides in synovial fluid and peripheral blood, to examine the CD8(+) T cell response against Chlamydia trachomatis antigens in nine patients with Chlamydia-triggered reactive arthritis (CtReA). Four of six HLA-B27(+) Ct-ReA patients had specific synovial T cell binding to at least one HLA-B27/Chlamydia peptide tetramer. The HLA-B27/Chlamydia peptide 195 tetramer bound to synovial T cells from three of six patients and HLA-B27/Chlamydia peptide 133 tetramer to synovial T cells from two patients. However, the frequency of these cells was low (0.02-0.09%). Moreover, we demonstrate two methods to generate HLA-B27-restricted T cell lines. First, HLA-B27 tetramers and magnetic beads were used to sort antigen-specific CD8(+) T cells. Second, Chlamydia-infected dendritic cells were used to stimulate CD8(+) T cells ex vivo. Highly pure CD8 T cell lines could be generated ex vivo by magnetic sorting by using HLA-B27 tetramers loaded with an EBV peptide. The frequency of Chlamydia-specific, HLA-B27 tetramer-binding CD8(+) T cells could be increased by stimulating CD8(+) T cells ex vivo with Chlamydia-infected dendritic cells. We conclude that HLA-B27 tetramers are a useful tool for the detection and expansion of HLA-B27-restricted CD8(+) T cells. T cells specific for one or more of three Chlamydia-derived peptides were found at low frequency in synovial fluid from HLA-B27(+) patients with Ct-ReA. These cells can be expanded ex vivo, suggesting that they are immunologically functional.
引用
收藏
页码:R521 / R534
页数:14
相关论文
共 35 条
[1]  
Allen RL, 1999, J IMMUNOL, V162, P5045
[2]   Phenotypic analysis of antigen-specific T lymphocytes [J].
Altman, JD ;
Moss, PAH ;
Goulder, PJR ;
Barouch, DH ;
McHeyzerWilliams, MG ;
Bell, JI ;
McMichael, AJ ;
Davis, MM .
SCIENCE, 1996, 274 (5284) :94-96
[3]   GUILT BY ASSOCIATION - HLA-B27 AND ANKYLOSING-SPONDYLITIS [J].
BENJAMIN, R ;
PARHAM, P .
IMMUNOLOGY TODAY, 1990, 11 (04) :137-142
[4]   Lymphoblastoid cells express HLA-1327 homodimers both intracellularly and at the cell surface following endosomal recycling [J].
Bird, LA ;
Peh, CA ;
Kolinberger, S ;
Elliott, T ;
McMichael, AJ ;
Bowness, P .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2003, 33 (03) :748-759
[5]  
Boisgérault F, 1998, INFECT IMMUN, V66, P4484
[6]  
Bowness P, 1998, EUR J IMMUNOL, V28, P2704, DOI 10.1002/(SICI)1521-4141(199809)28:09<2704::AID-IMMU2704>3.0.CO
[7]  
2-B
[8]   REITERS DISEASE AND HL-A 27 [J].
BREWERTON, DA ;
NICHOLLS, A ;
OATES, JK ;
CAFFREY, M ;
WALTERS, D ;
JAMES, DCO .
LANCET, 1973, 2 (7836) :996-998
[9]   DIFFERENT HLA-B27 SUBTYPES PRESENT THE SAME IMMUNODOMINANT EPSTEIN-BARR-VIRUS PEPTIDE [J].
BROOKS, JM ;
MURRAY, RJ ;
THOMAS, WA ;
KURILLA, MG ;
RICKINSON, AB .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 178 (03) :879-887
[10]   Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers [J].
Day, CL ;
Seth, NP ;
Lucas, M ;
Appel, H ;
Gauthier, L ;
Lauer, GM ;
Robbins, GK ;
Szczepiorkowski, ZM ;
Casson, DR ;
Chung, RT ;
Bell, S ;
Harcourt, G ;
Walker, BD ;
Klenerman, P ;
Wucherpfennig, KW .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 112 (06) :831-842