Normal T cell receptor V beta usage in a primary immunodeficiency associated with HLA class II deficiency.
The human T cell receptor was studied using an anchored-polymerase chain reaction (A-PCR) and hybridization with V beta-specific oligonucleotide probes, together with the few anti-V beta monoclonal antibodies (mAb) available. After confirming the semiquantitative and reproducible nature of the A-PCR technique, we assessed the complete V beta repertoire in sorted CD4+ and CD8+ lymphocyte populations from three normal donors. These experiments confirmed the absence of V beta-restricted deletions in human peripheral cells, in contrast to several mouse strains. This feature makes it difficult to study negative selection in man, given the apparent absence of an endogenous superantigen corresponding to the Mls system in the mouse. To investigate human V beta repertoire shaping, we studied V beta usage in CD4+ and CD8+ T cells from children with an inherited immunodeficiency characterized by defective expression of human leukocyte antigen class II molecules. An initial study using anti-V beta monoclonal antibodies failed to show significant abnormalities in V beta usage. Four patients analyzed using the A-PCR method all had a polyclonal V beta repertoire, suggesting normal positive selection and raising questions as to the importance of V beta major histocompatibility complex (MHC) interactions and the role of thymic MHC density in shaping the V beta repertoire.
Rieux-Laucat
F
F
INSERM U132, Hôpital Necker-Enfants Malades, Paris, France.
Le Deist
F
F
Selz
F
F
Fischer
A
A
de Villartay
J P
JP
D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D015870:Gene Expression; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D005796:Genes; D006681:HLA-D Antigens / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000502:physiology*
D006681:HLA-D Antigens; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta