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

摘要

Previously, we and others have shown that MHC class-II deficient humans have greatlyreduced numbers of CD4+CD8– peripheral T cells. These type-III Bare LymphocyteSyndrome patients lack MHC class-II and have an impaired MHC class-I antigenexpression. In this study, we analyzed the impact of the MHC class-II deficientenvironment on the TCR V-gene segment usage in this reduced CD4+CD8– T-cellsubset. 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 foreach of the most known V α- and V ß;-gene region families. The results of our studiesdemonstrate that some of the V α-gene segments are used less frequent in theCD4+CD8– T-cell subset of the patient, whereas the majority of the TCR V α- andV ß-gene segments investigated were used with similar frequencies in both subsets in thetype-III Bare Lymphocyte Syndrome patient compared to healthy control familymembers. Interestingly, the frequency of TcR V α12 transcripts was greatly diminishedin 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. Onthe basis of the results obtained in this study, it is concluded that within the reducedCD4+CD8– T-cell subset of this patient, most of the TCR V-gene segments tested for areemployed. However, a skewing in the usage frequency of some of the V α-gene segmentstoward the CD4–CD8+ T-cell subset was noticeable in the MHC class-II deficient patientthat differed from those observed in the healthy family controls.