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 dire cted against autologous cancer cells. One of the surrogate markers for suce ssful immunization is the 'structural' characterization of T-lymphocytes re acting to the immunizing peptide as determined by CDR3-length and DNA-seque nce analysis. Most of the recent studies examining ex vivo T-cell reponses in patients with cancer have focussed on expression and prevalence of the T CR beta variable region, predominantly in non-sorted T-cell populations. He re, 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 speci mens obtained from patients with cervical cancer. We suggest that a detaile d analysis of the TCR-repertoire in patients undergoing 'epitope-based' imm unotherapy, 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 stu dies should be performed on CD4(+) or CD8(+) sorted T-cells or, if tissue s pecimens are analyzed, should be accompanied by a CD4 and CD8 staining.