Multispecific CD4+ T cell response to a single 12-mer epitope of the immunodominant heat-shock protein 60 of Yersinia enterocolitica in Yersinia-triggered reactive arthritis: overlap with the B27-restricted CD8 epitope, functional properties, and epitope presentation by multiple DR alleles.
Yersinia heat-shock protein 60 (Ye-hsp60) has recently been found to be a dominant CD4 and CD8 T cell Ag in Yersinia-triggered reactive arthritis. The nature of this response with respect to the epitopes recognized and functional characteristics of the T cells is largely unknown. CD4+ T cell clones specific for Ye-hsp60 were raised from synovial fluid mononuclear cells from a patient with Yersinia-triggered reactive arthritis. and their specificity was determined using three recombinant Ye-hsp60 fragments, overlapping 18-mer synthetic peptides as well as truncated peptides. Functional characteristics were assessed by cytokine secretion analysis in culture supernatants after specific antigenic stimulation. Amino acid positions relevant for T cell activation were detected by single alanine substitutions within the epitopes. Fragment II comprising amino acid sequence 182-371 was recognized by the majority of clones. All these clones were specific for peptide 319-342. Th1 clones and IL-10-secreting clones occurred in parallel, sometimes with the same fine specificity. The 12-mer core epitope 322-333 is a degenerate MHC binder and is presented to some T cell clones in a "promiscuous" manner. This epitope is almost identical with a B27-restricted CTL epitope of Ye-hsp60. Cross-reactivity of Ye-hsp60-specific T cell clones with self-hsp60 was not observed. In conclusion, an interesting Ye-hsp60 T cell epitope has been identified and characterized. It remains to be determined whether this epitope is also relevant in other reactive arthritis patients.
Mertz
A K
AK
Department of Medicine II, University Hospital, Ulm, Germany. akhmertzet-online.de
Wu
P
P
Sturniolo
T
T
Stoll
D
D
Rudwaleit
M
M
Lauster
R
R
Braun
J
J
Sieper
J
J
D000293:Adolescent; D000328:Adult; D000409:Alanine / Q000235:genetics; D000483:Alleles; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D017951:Antigen Presentation / Q000276:immunology*; D016918:Arthritis, Reactive / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D001667:Binding, Competitive / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015796:HLA-B27 Antigen / Q000276:immunology* / Q000502:physiology; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D015009:Yersinia Infections / Q000276:immunology; D015008:Yersinia enterocolitica / Q000276:immunology*
D001426:Bacterial Proteins; D018834:Chaperonin 60; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015796:HLA-B27 Antigen; D006684:HLA-DR Antigens; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D000409:Alanine