Identification of type II collagen peptide 261–273-specific T cell clones in a patient with relapsing polychondritis
✍ Scribed by Jane H. Buckner; Megan Van Landeghen; William W. Kwok; Laura Tsarknaridis
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 140 KB
- Volume
- 46
- Category
- Article
- ISSN
- 0004-3591
No coin nor oath required. For personal study only.
✦ Synopsis
Objective. To characterize and clone T cells specific for type II collagen (CII) in a patient with relapsing polychondritis (RP) and to establish whether the immunodominant epitope of CII determined in HLA transgenic mice is used in the human autoimmune response to CII. Methods. T cell responses to CII were examined in a patient with RP, who was heterozygous for the HLA-DR allele DRB1*0101/DRB1*0401. T cell clones were established from this patient and characterized for peptide specificity, class II restriction, cytokine production, and staining with HLA-DRB1*0401 class II tetramers. Results. A response to CII and the peptide 255-273 was present in this patient. T cells specific for the CII epitope 261-273 were cloned. Evaluation of these clones demonstrated a response to CII 261-273 in the context of both DR alleles. HLA-DR4 CII tetramer did not demonstrate staining of either CII-specific DRB1*0401-restricted T cell clones or a polyclonal population of CII-reactive T cells from this individual. Conclusion. T cells directed against CII were present in this patient with RP. Also, T cell clones isolated from this individual were found to be specific for the CII peptide 261-273 and were restricted to either the DRB1*0101 or the DRB1*0401 allele. These findings establish that a T cell response directed against CII is present in this patient with RP and that the CII peptide 261-273 plays a role in the human immune response to CII.
Type II collagen (CII) is the predominant protein found in hyaline cartilage and is a candidate autoantigen in relapsing polychondritis (RP), in which inflammation and destruction of cartilage are predominant features. Antibodies directed toward CII are present in the majority of patients with RP, suggesting its importance as an autoantigen in these individuals (1-3), and immunization with CII leads to chondritis in several animal models (4-7). However, the T cell response to CII in patients with RP has not been clearly demonstrated. Due to the cartilage-specific nature of RP and our knowledge of the potential CII epitopes involved in the immune response to CII, we hypothesized that an autoimmune response to CII and peptides derived from CII may be demonstrable in an individual with RP.
In this study, we demonstrate a T cell response directed against CII in a DRB1*0101/0401 heterozygous patient with RP. T cell clones isolated from this individual were found to be specific for the CII peptide 261-273, a peptide identified as immunodominant in HLA transgenic mice and restricted to either the DRB1*0101 or DRB1*0401 allele (8-10). These findings demonstrate that T cells specific for CII 261-273 can be found in humans and raise the possibility that these autoreactive T cells play a role in disease.
PATIENTS AND METHODS
Clinical history. The patient, a 43-year-old white man, had a history of RP since the age of 20. The diagnosis was based on the development of a saddlenose deformity at age 22, auricular chondritis at age 34, and associated hoarseness, as well as costochondritis and arthritis of the small joints. Laboratory findings included normal blood cell counts and chemistry panels, an elevated erythrocyte sedimentation rate during RP flares, the absence of antinuclear antibodies and rheumatoid factor, and the presence of IgG antibodies to CII. There was no evidence of infection or malignancy.