The V beta 17+ T cell repertoire: skewed J beta usage after thymic selection; dissimilar CDR3s in CD4+ versus CD8+ cells.
To ascertain how the actual repertoire of T cell receptors (TCRs) deviates from the theoretical, we have generated a large number of junctional region sequences from TCRs carrying the V beta 17 variable region. The greater than 600 sequences analyzed represent transcripts from nine different cell populations, permitting several comparisons: transcripts from an expressed vs. a non-expressed V beta 17 allele, those from E+ vs. E- mice, transcripts from immature vs. mature thymocytes, those from thymic vs. peripheral T cells, and those from CD4+ vs. CD8+ cells. These comparisons have allowed us to distinguish between the influence of molecular events involved in TCR gene rearrangement and that of various selection events that shape the T cell repertoire. Our most striking findings are: (a) that J beta usage is markedly skewed, partly due to recombination mechanics and partly due to selection forces: in particular, those mediated by the class II E molecule in the thymus; and (b) that TCRs on CD4+ and CD8+ cells show intriguing dissimilarities. In addition, we present evidence that N nucleotide additions occur with clear biases, probably due to idiosyncrasies of the recombination enzymes, and provide arguments that TCR and immunoglobulin CDR3s have distinct structures.
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, l'INSERM, Strasbourg, France.
S
S
Candéias
C
C
Waltzinger
C
C
Benoist
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D
Mathis
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis*; D007135:Immunoglobulin Variable Region; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000032:analysis* / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000502:physiology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell