ORIGINAL ARTICLE

Lung restricted T cell receptor AV2S3+ CD4+ T cell expansions in sarcoidosis patients with a shared HLA-DRß chain conformation

J Grunewald¹, J Wahlström², M Berlin¹, H Wigzell², A Eklund¹ and O Olerup³

¹ Department of Medicine, Division of Respiratory Medicine, Karolinska Hospital and Karolinska Institutet, Stockholm, Sweden
² Microbiology and Tumorbiology Center (MTC), Karolinska Institutet, Stockholm, Sweden
³ Department of Biosciences at Novum and Division of Clinical Immunology, Huddinge Hospital, Huddinge and Karolinska Institutet, Stockholm, Sweden

Correspondence to:
Correspondence to:
Dr J Grunewald, Department of Medicine, Division of Respiratory Medicine, Lung Research Laboratory L2:01, Karolinska Hospital, 171 76 Stockholm, Sweden;
johan.grunewald{at}medks.ki.se

Background: Sarcoidosis is a systemic disease of unknown aetiology frequently affecting the lungs. CD4+ T cells, in particular, accumulate in the lungs, implicating them in the pathogenesis of the disease.

Methods: T cell receptor (TCR) variable (V) gene expression on bronchoalveolar lavage (BAL) fluid T cells and the HLA DR alleles of 121 Scandinavian patients with sarcoidosis was determined.

Results: As expected from our previous results, almost every DRB1*0301 (i.e. DR17) positive patient (67/69) had significantly increased numbers of AV2S3+ CD4+ T cells in the BAL fluid but normal levels in peripheral blood (that is, lung restricted expansions) compared with only six of 52 DRB1*0301 negative patients. Detailed genotypic HLA analysis showed that these six DRB1*0301 negative patients with lung restricted AV2S3+ T cell expansions had another HLA allele in common—the HLA-DRB3*0101 allele (also called DR52a)—which was not found in any other DRB1*0301 negative patient. A new group of sarcoidosis patients was therefore identified, characterised by a strict correlation between a distinct HLA allele and lung accumulated T cells expressing a particular TCR V segment. Furthermore, the HLA-DRB1*0301 and HLA-DRB3*0101 encoded molecules showed similarities, with identical amino acid sequences in regions important for antigen binding which may enable them to bind and present the same or similar antigenic peptides.

Conclusions: HLA-DRB3*0101 as well as DRB1*0301 positive sarcoidosis patients may have the capacity to present specific sarcoidosis associated antigens in such a way that AV2S3+ CD4+ T cells are stimulated preferentially, generating lung restricted AV2S3+ T cell expansions.

Keywords: T cell receptor; HLA; bronchoalveolar lavage; sarcoidosis

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Jonth, A. C., Silveira, L., Fingerlin, T. E., Sato, H., Luby, J. C., Welsh, K. I., Rose, C. S., Newman, L. S., du Bois, R. M., Maier, L. A., The ACCESS Group, (2007). TGF-beta1 Variants in Chronic Beryllium Disease and Sarcoidosis. J. Immunol. 179: 4255-4262 [Abstract] [Full Text]  
• Grunewald, J., Eklund, A. (2007). State of the Art. Role of CD4+ T Cells in Sarcoidosis. Proc Am Thorac Soc 4: 461-464 [Abstract] [Full Text]  
• Idali, F., Wiken, M., Wahlstrom, J., Mellstedt, H., Eklund, A., Rabbani, H., Grunewald, J. (2006). Reduced Th1 response in the lungs of HLA-DRB1*0301 patients with pulmonary sarcoidosis.. Eur Respir J 27: 451-459 [Abstract] [Full Text]  
• Grunewald, J., Eklund, A., Olerup, O. (2004). Human Leukocyte Antigen Class I Alleles and the Disease Course in Sarcoidosis Patients. Am. J. Respir. Crit. Care Med. 169: 696-702 [Abstract] [Full Text]  
• Planck, A., Eklund, A., Grunewald, J. (2003). Markers of activity in clinically recovered human leukocyte antigen-DR17-positive sarcoidosis patients. Eur Respir J 21: 52-57 [Abstract] [Full Text]