Clonal dominance and selection for similar complementarity determining region 3 motifs among T lymphocytes responding to the HLA-DR3-associated Mycobacterium leprae heat shock protein 65-KD peptide 3–13

In order to establish whether specific MHC class II-peptide complexes are capable of selecting TCR V regions, we investigated in detail the TCR β chain used in the recognition of HLA-DR3 restricted hsp65 peptide 3–13 in a tuberculoid leprosy patient. Using RT-PCR, a clear dominance of the TCRBV5 gene family was observed in a hsp65 peptide 3–13-specific T-cell line; however, not in fresh, unstimulated PBMCs, PHA-stimulated PBMCs, or a T-cell line specific for tetanus toxoid.

DNA sequence analysis of the TCR V regions, comprising TCRBV5 genes, derived from the hsp65 peptide 3–13-specific T-cell line revealed the exclusive usage of the TCRBV5S1 gene segment and a predominance of one V-D-J gene rearrangement, which is indicative of clonal expansion of these T lymphocytes. Additional highly similar V-D-J gene rearrangements were detected at a low level in this hsp65 peptide 3–13-specific T-cell line. These conserved junctional regions (CDR3 regions) could not be detected within the TCRBV5 gene family of fresh PBMCs, PHA-stimulated PBMCs, hsp65, and tetanus-toxoid-specific T-cell lines from this patient.

The observations in this tuberculoid leprosy patient reveal that an HLA class-II-restricted T-cell response results in selection of TCRBV regions which are highly similar in amino acid composition to the CDR3 region within the expanding TCRBV regions.