T cell receptor beta-chain third complementarity-determining region gene usage is highly restricted among Sm-B autoantigen-specific human T cell clones derived from patients with connective tissue disease.
OBJECTIVE
To determine the structure of T cell receptors (TCR) used by Sm-B-reactive human T cell clones, to map T cell epitopes on the Sm-B autoantigen, and to determine the HLA restriction element used in the recognition of Sm-B by T cells.


METHODS
Sm-B-reactive T cell clones were generated from patients with connective tissue disease by using either a recombinant fusion protein or synthetic peptides. The TCR structure was defined with the use of polymerase chain reaction and DNA sequencing. Synthetic peptides were used to map T cell epitopes on Sm-B. HLA restriction element usage was defined by using monoclonal antibody blocking.


RESULTS
Usage of the TCR third complementarity-determining region (CDR3) was highly restricted among Sm-B autoantigen-specific human T cell clones. Only amino acids 48-96 of the Sm-B2 autoantigen were recognized by T cells, and this occurred in the context of HLA-DR.


CONCLUSIONS
TCR CDR3 gene usage is highly conserved by Sm-B autoantigen-specific T cell clones, and this appears to be related to the recognition of a limited number of T cell epitopes on the Sm-B autoantigen presented in the context of HLA-DR.
Talken
B L
BL
University of Missouri, and Department of Veterans Affairs, Harry S Truman Memorial Veterans Hospital, Columbia, USA.
Holyst
M M
MM
Lee
D R
DR
Hoffman
R W
RW
D000595:Amino Acid Sequence; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002999:Clone Cells; D003240:Connective Tissue Diseases / Q000235:genetics / Q000276:immunology*; D018604:Epitope Mapping; D015870:Gene Expression / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D055517:snRNP Core Proteins
D001324:Autoantigens; D017252:CD3 Complex; D006684:HLA-DR Antigens; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins