TCR V α- and V ß-Gene Segment Use in T-Cell Subcultures Derived from a Type-III Bare Lymphocyte Syndrome Patient Deficient in MHC Class-II Expression

Previously, we and others have shown that MHC class-II deficient humans have greatly reduced numbers of CD4+CD8– peripheral T cells. These type-III Bare Lymphocyte Syndrome patients lack MHC class-II and have an impaired MHC class-I antigen expression. In this study, we analyzed the impact of the MHC class-II deficient environment on the TCR V-gene segment usage in this reduced CD4+CD8– T-cell subset. For these studies, we employed TcR V-region-specific monoclonal antibodies (mAbs) and a semiquantitative PCR technique with V α and V ß amplimers, specific for each of the most known V α- and V ß;-gene region families. The results of our studies demonstrate that some of the V α-gene segments are used less frequent in the CD4+CD8– T-cell subset of the patient, whereas the majority of the TCR V α- and V ß-gene segments investigated were used with similar frequencies in both subsets in the type-III Bare Lymphocyte Syndrome patient compared to healthy control family members. Interestingly, the frequency of TcR V α12 transcripts was greatly diminished in the patient, both in the CD4+CD8– as well as in the CD4–CD8+ compartment, whereas this gene segment could easily be detected in the healthy family controls. On the basis of the results obtained in this study, it is concluded that within the reduced CD4+CD8– T-cell subset of this patient, most of the TCR V-gene segments tested for are employed. However, a skewing in the usage frequency of some of the V α-gene segments toward the CD4–CD8+ T-cell subset was noticeable in the MHC class-II deficient patient that differed from those observed in the healthy family controls.