The Journal of Immunology, Vol 155, Issue 5 2329-2338, Copyright © 1995 by American Association of Immunologists

ARTICLES

Marked conservation of complementarity-determining region 3 of the beta- chain of TCRs recognizing a mycobacterial heat shock protein 60-derived peptide with strong sequence similarity to human heat shock protein 60

JC Goodall, J Henwood, PA Bacon and JS Gaston
Department of Rheumatology, Medical School, Birmingham University, United Kingdom.

The variable gene usage and sequence of human TCRs specific for a particular MHC/peptide combination have been investigated. The peptide comprises amino acids 456-466 of the 65-kDa Mycobacterium tuberculosis heat shock protein (hsp60), and is recognized in the context of HLA-DP. TCRs from both synovial fluid and peripheral blood (PB)-derived T cell clones used only five different V beta genes, three of which are closely related (V beta 6.7a, V beta 6.7b, and V beta 21.3). Among TCRs using these three genes there was marked conservation of the beta-chain sequence, whereby complementarity-determining region 3 (CDR3) contained an amino acid motif (*R*G*, amino acids 96-100) in association with either J beta 1.4 or J beta 2.5. These conclusions were strengthened by analysis of peptide-stimulated T cell lines that revealed not only TCR beta-chain sequences identical with those seen in T cell clones, but also additional beta-chains with similar CDR3 region sequences and J gene usage. In contrast, T cell lines derived by using IL-2 or a control peptide revealed variable usage of V beta and J beta genes; V beta 6.7a/b sequences from these lines and from freshly isolated PB did not contain the CDR3 motif noted in TCRs from Ag-specific T cells. We suggest that the remarkably limited diversity of TCRs noted in this study is a consequence of the similarity between the mycobacterial hsp60 peptide and the equivalent peptide from human hsp60, and reflects the trimming of the TCR repertoire required to maintain self-tolerance.

This article has been cited by other articles:

				H. R. Kim, E. Y. Kim, J. Cerny, and K. D. Moudgil Antibody Responses to Mycobacterial and Self Heat Shock Protein 65 in Autoimmune Arthritis: Epitope Specificity and Implication in Pathogenesis J. Immunol., November 15, 2006; 177(10): 6634 - 6641. [Abstract] [Full Text] [PDF]

				J. Grunewald, E. Halapi, J. Wahlstrom, R. Giscombe, S. Nityanand, C. Sanjeevi, and A.-K. Lefvert T-Cell Expansions With Conserved T-Cell Receptor beta  Chain Motifs in the Peripheral Blood of HLA-DRB1*0401 Positive Patients With Necrotizing Vasculitis Blood, November 15, 1998; 92(10): 3737 - 3744. [Abstract] [Full Text] [PDF]

				J. C. Steele, S. P. Young, J. C. Goodall, and P. H. Gallimore Structural Aspects of the Interaction Between Heterogeneic Human Papillomavirus Type 1 E4-Specific T Cell Receptors and the Same Peptide/HLA-DQ8 Complex J. Immunol., November 1, 1998; 161(9): 4745 - 4752. [Abstract] [Full Text] [PDF]