[HTML][HTML] Restricted Usage of T Cell Receptor Vα/Jα Gene Segments with Different Nucleotide but Identical Amino Acid Sequences in HLA-DR3+ Sarcoidosis …
J Grunewald, T Hultman, A Bucht, A Eklund… - Molecular Medicine, 1995 - Springer
J Grunewald, T Hultman, A Bucht, A Eklund, H Wigzell
Molecular Medicine, 1995•SpringerBackground Sarcoidosis is a granulomatous disease characterized by the accumulation of
activated T cells in the lungs. We previously showed that sarcoidosis patients expressing the
HLA haplotype DR3 (17), DQ2 had increased numbers of lung CD4+ T cells using the T cell
receptor (TCR) variable region (V) α 2.3 gene segment product. In the present study, the
composition of both the TCR α-and β-chains of the expanded CD4+ lung T cells from four
DR3 (17), DQ2+ sarcoidosis patients was examined. Materials and Methods TCR α-chains …
activated T cells in the lungs. We previously showed that sarcoidosis patients expressing the
HLA haplotype DR3 (17), DQ2 had increased numbers of lung CD4+ T cells using the T cell
receptor (TCR) variable region (V) α 2.3 gene segment product. In the present study, the
composition of both the TCR α-and β-chains of the expanded CD4+ lung T cells from four
DR3 (17), DQ2+ sarcoidosis patients was examined. Materials and Methods TCR α-chains …
Background
Sarcoidosis is a granulomatous disease characterized by the accumulation of activated T cells in the lungs. We previously showed that sarcoidosis patients expressing the HLA haplotype DR3(17), DQ2 had increased numbers of lung CD4+ T cells using the T cell receptor (TCR) variable region (V) α 2.3 gene segment product. In the present study, the composition of both the TCR α- and β-chains of the expanded CD4+ lung T cells from four DR3(17), DQ2+ sarcoidosis patients was examined.
Materials and Methods
TCR α-chains were analyzed by cDNA cloning and nucleotide sequencing. TCR β-chains were analyzed for Vβ usage by flow cytometry using TCR V-specific monoclonal antibodies or by the polymerase chain reaction (PCR) using Vβ- and Cβ-specific primers. Jβ usage was analyzed by Southern blotting of PCR products and subsequent hybridization with radiolabeled Jβ-specific probes.
Results
Evidence of biased Jα gene segment usage by the α-chains of Vα 2.3+ CD4+ lung T cells was found in four out of four patients. Both different α-chain nucleotide sequences coding for identical amino acid sequences and a number of identically repeated α-chain sequences were identified. In contrast, the TCR β-chains of FACS-sorted Vα 2.3+ CD4+ lung T cells were found, with one exception, to have a nonrestricted TCR Vβ usage.
Conclusions
The finding of Vα 2.3+ CD4+ lung T cells with identical TCR α-chain amino acid sequences but with different nucleotide sequences strongly suggests that different T cell clones have been selected to interact with a specific sarcoidosis associated antigen(s). The identification of T cells with restricted TCR usage, which may play an important role in the development of sarcoidosis, and the possibility of selectively manipulating these cells should have important implications for the treatment of the disease.
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