Monoclonal TCR mRNA transcripts are preferentially detected in the TCR variable alpha chain in CD8(+) T-lymphocytes: implications for immunomonitoring.

Clinical trials have started to implement tumor-associated antigens in the form of antigenic peptides in order to augment CD8(+) T-cell responses directed against autologous cancer cells. One of the surrogate markers for successful immunization is the characterization of T-lymphocytes reacting to the immunizing peptide as determined by CDR3-length and DNA-sequence analysis. Most of the recent studies examining ex vivo T-cell responses in patients with cancer have focussed on expression and prevalence of the TCR Beta variable region, predominantly in non-sorted T-cell populations. Here, we show that clonal T-cell receptors (TCRs), as defined by DNA-fragment analysis and DNA-sequencing, appear to be predominantly present in the CD8(+) T-cell population and that these clonal TCRs are preferentially TCR-VA chains. This has been found to be true for PBL obtained from normal healthy subjects or from patients suffering from cancer, as well is in tumor specimens obtained from patients with cervical cancer. We suggest that a detailed analysis of the TCR-repertoire in patients undergoing immunotherapy, should include: i) examination of both TCR VA and VB families. ii) The absence of TCR VA or VB families should be noted and iii) these studies should be performed on CD4(+) or CD8(+) sorted T-cells or, if tissue specimens are analyzed, should be accompanied by a CD4 and CD8 staining.