Functional consequences of a T cell receptor D beta 2 and J beta 2 gene segment deletion.
The TCR beta-chain locus of NZW mice carries an 8.8-kb deletion which encompasses the C beta 1, D beta 2, and all six J beta 2 gene segments. On a theoretical basis, the absence of D beta 2 and J beta 2 gene segments in this strain should result in a 70% reduction of the diversity of the TCR repertoire. To experimentally assess the effects of this deletion, we bred the NZW TCR beta-chain allele onto a BALB/c background and tested the ability of this new congenic strain to respond to a panel of 22 random Ag. T cells from BALB/c.beta NZW mice responded to all 22 Ag tested but the magnitude of the response to a large proportion of these Ag (11 of 22) was markedly reduced when compared with T cells from BALB/c mice. Responses to the remaining Ag were either comparable (9 of 22) or occasionally even enhanced (2 of 22) compared with BALB/c mice. In addition, we found that the frequency of V beta 6- and V beta 8.1-bearing T cells was increased by approximately 20% in BALB/c.beta NZW mice. These results suggest that D beta 2 and J beta 2 gene segments are required to maintain a diverse T cell repertoire and that their deletion from the genome may confer a significant selective disadvantage in the wild.
Woodland
D L
DL
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80262.
Kotzin
B L
BL
Palmer
E
E
D000818:Animals; D015139:Blotting, Southern; D002872:Chromosome Deletion; D005796:Genes; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D008912:Minor Histocompatibility Loci; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000502:physiology*; D014301:Trinitrobenzenes / Q000276:immunology
D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014301:Trinitrobenzenes