Analysis of the T cell receptor in the lymphoproliferative disease of granular lymphocytes: superantigen activation of clonal CD3+ granular lymphocytes.
To investigate whether cell populations in CD3+ lymphoproliferative disease of granular lymphocytes (LDGLs) were skewed toward the use of specific V beta regions, we studied the repertoire of T-cell receptor (TCR) V beta gene products in 18 patients, as well as their relationship to the clonal bands in the Southern blot and the activation mediated by superantigens. Using a panel of monoclonal antibodies (mAbs) for conserved V beta segments and PCR, a dominant population expressing a specific V beta region was demonstrated in all patients. In five (27%) cases, granular lymphocytes (GLs) were found to express the V beta 13.1, while V beta 8 and V beta 6 were each expressed in three (17%) cases. The remaining cases were characterized by the proliferation of TCR V beta 2, V beta 3, V beta 4, V beta 9, V beta 12, V beta 16, and V beta 20. This finding indicates a biased usage of a limited TCR V beta in LDGLs, since nearly 60% of the cases utilized only three families of the TCR V beta genes. In all of the cases studied, we proved that the subset recognized by mAb and PCR was identical to that accounting for the extra band(s) of the Southern blot. This finding confirms the clonal nature of the population identified according to TCR V beta expression both by phenotype and PCR. On functional grounds, we evaluated whether GLs can be activated through the specific TCR using the superantigens recognizing discrete V beta families, such as staphylococcal proteins, including SEA, SEB, SEC1, SEC2, SED, and SEE. We demonstrated that the TCR-alpha/beta of clonal GLs in LDGL patients is functionally active in delivering cytotoxic and proliferative signals upon superantigen activation.
Department of Clinical and Expedrimental Medicine, Padua University School of Medicine, Italy.
R
R
Zambello
L
L
Trentin
M
M
Facco
A
A
Cerutti
R
R
Sancetta
A
A
Milani
R
R
Raimondi
C
C
Tassinari
C
C
Agostini
G
G
Semenzato
D017252:CD3 Complex / Q000032:analysis*; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism*; D018089:Superantigens / Q000276:immunology*
D017252:CD3 Complex; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens