Affinity maturation of lymphocyte receptors and positive selection of T cells in the thymus.
In this review we have re-evaluated the dominant paradigm that TcR V genes do not somatically mutate. We highlight the many structural and functional similarities between Ig and TcR antigen-specific receptors on B and T cells. We have reviewed the factors influencing the somatic and germline evolution of IgV regions in B cells, have evaluated in detail various models which could be invoked to explain the pattern of variation in both transcribed and non-transcribed segments of germline IgV-gene DNA sequences, and applied this perspective to the TcR V beta and V alpha genes. Whilst specific TcRs recognize a complex of a short antigenic peptide bound to MHC Class I or II glycoprotein, and Ig receptors can recognize both oligopeptides and conformational determinants on undegraded polypeptides, they both employ heterodimer variable regions (Fabs) utilizing all three CDRs in epitope binding. We conclude that a plausible case can be made for the possibility that rearranged TcR V genes may undergo some type of somatic hypermutation process during T-cell development in the thymus (concurrent with or after the positive selection phase) thus allowing a repertoire of TvR alpha beta heterodimers to be both positively and negatively selected by the same set of ligands (self MHC + self peptide) in the thymus.
Steele
E J
EJ
Department of Biological Sciences, University of Wollongong, NSW, Australia.
Rothenfluh
H S
HS
Ada
G L
GL
Blanden
R V
RV
D000818:Animals; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology*
D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell