Multispecific CD4+ T Cell Response to a Single 12-mer Epitope of the Immunodominant Heat-Shock Protein 60 ofYersinia enterocoliticainYersinia-Triggered Reactive Arthritis: Overlap with the B27-Restricted CD8 Epitope, Functional Properties, and Epitope Presentation by Multiple DR Alleles

Abstract

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.

The Major Histocompatibility Complex Class II AllelesMamu-DRB1*1003and -DRB1*0306Are Enriched in a Cohort of Simian Immunodeficiency Virus-Infected Rhesus Macaque Elite Controllers

“…1B and Table 2). The Vpx [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] VE15-specific CD4 ϩ T-cell response was further mapped to two peptides, Vpx 31-40 EL10 and Vpx 32-41 IP10 (Fig. 2D and Table 2).…”

“…Peptides of 10 or 11 amino acids in length were used to map each SIV-specific CD4 ϩ T-cell line or clone. Gag 97-111 TE15/Gag 101-115 KT15 was mapped with peptides of 10 amino acids in length (A), Gag 181-195 CD15 was mapped using peptides of 10 amino acids in length (B), Gag 197-211 QA15 was mapped using peptides of 11 amino acids in length (C), Vpx [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] VE15 was mapped with peptides of 10 amino acids in length (D), Rev 9-23 ET15/Rev 13-27 RY15 was mapped with peptides of 11 amino acids in length (E), and Nef 138-152 RI15 was mapped using peptides of 10 amino acids in length (F). The IFN-␥ production was normalized for each SIV-specific CD4…”

Renal cell carcinoma–associated antigen G250 encodes a naturally processed epitope presented by human leukocyte antigen‐dr molecules to CD4+ T lymphocytes

“…9 Overlapping CD4 ϩ and CD8 ϩ T-cell epitopes have been described in experimental models of influenza, p53, HIV, ras and heat-shock protein 60. [23][24][25][26] Besides G250, the tumor-specific antigens mucin-1 and prostate-specific antigen also contain peptides with both MHC class I and class II motifs. [27][28][29] Such long peptides that contain both class I and class II motifs could be promising tools to treat cancer patients.…”

Immune regulation in adjuvant‐induced arthritis: Possible implications for innovative therapeutic strategies in arthritis

“…So far, none of the proteins identified by these 2 approaches has been a component of cartilage, and none has been tested for arthritogenic activity. It is relevant that Hsp60 is the dominant epitope recognized by CD4ϩ and CD8ϩ T cells in reactive arthritis following Yersinia or other gram-negative enteric infections (35,36). Conversely, the epitope incriminated in both Klebsiella pneumoniae-related reactive arthritis and ankylosing spondylitis is a peptide of the enzyme nitrogenase, which is strongly expressed in the joint synovia (60,61).…”

“…The dominant epitope recognized by pathogenic CD4ϩ and CD8ϩ T cells in, for example, Yersiniatriggered disease, is Hsp60 (36). Synovial CD4ϩ T cell clones from such cases recognize a 12-mer epitope (peptide 322-333) of Yersinia Hsp60, presented by multiple DR alleles, which overlaps a B27-restricted CD8ϩ T cell epitope.…”