Molecular genetic analysis of 178 I-Abm12-reactive T cells.
We have studied the genetic diversity of the TCR repertoire to the murine alloantigen I-Abm12 by generating a panel of 178 C57BL/10-derived I-Abm12-reactive T cell hybridomas. The expression of V alpha and V beta gene families was examined in this panel and the frequency of expression of V beta, but not ofV alpha, gene families differed significantly from that observed in a companion panel of random C57BL/10-derived hybridomas. The V beta 5 gene family was expressed significantly less frequently while the V beta 14, V beta 15, and V beta 16 genes were expressed significantly more frequently in the panel of I-Abm12-reactive than in the panel of random hybridomas. The junctional regions (VJ alpha and VDJ beta) of TCR V alpha and V beta genes from selected I-Abm12-specific hybridomas were amplified using the polymerase chain reaction, and directly sequenced. Surprisingly, no conserved J alpha, D beta, J beta, or N region-encoded sequences among these selected I-Abm12-reactive TCRs were identified. Thus, the T cell response to an I-A alloantigen that differs by only three amino acid residues from the I-A molecule of the responding strain is genetically complex but nonrandom. We have estimated that the repertoire to this alloantigen is comprised of at least 37 different TCRs.
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
J
J
Bill
J
J
Yagüe
V B
VB
Appel
J
J
White
G
G
Horn
H A
HA
Erlich
E
E
Palmer
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015342:DNA Probes; D005784:Gene Amplification; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D005810:Multigene Family; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
D015342:DNA Probes; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell