| First Author | Sim BC | Year | 2003 |
| Journal | Immunogenetics | Volume | 54 |
| Issue | 12 | Pages | 874-83 |
| PubMed ID | 12671739 | Mgi Jnum | J:83452 |
| Mgi Id | MGI:2662045 | Doi | 10.1007/s00251-002-0532-y |
| Citation | Sim BC, et al. (2003) Surprisingly minor influence of TRAV11 (Valpha14) polymorphism on NK T-receptor mCD1/alpha-galactosylceramide binding kinetics. Immunogenetics 54(12):874-83 |
| abstractText | Defects in natural killer T (NK T) cell function and of interleukin-4 -production in SJL and NOD mice have been linked to susceptibility to autoimmune disease. As SJL and NOD mice both carry the T-cell receptor (TCR) alpha-chain locus 'c' (Tcra(c)) haplotype, found in few other strains, we have attempted to determine the influence of Tcra polymorphism on NK T-cell recognition of ligand, selection, and immune responses. The majority of NK T cells use an 'invariant' TRAV11J15 (previously called AV14J18 or Valpha14 Jalpha281) alpha- chain paired with either TRBV13-2, BV29, or BV1 to recognize ligands presented by mCD1 molecules, including the glycolipid alpha-galactosylceramide (alpha-GalCer). Sequencing of TRAV11 from the mouse strains B10.A (encoding the Tcra(b) haplotype), B10.A- Tcra(c), and NOD (Tcra(c)) shows that Tcra(c) has a single TRAV11 gene (TRAV11*01) and that Tcra(b) has a single expressed gene (TRAV11*02), plus a closely related pseudogene. There is no apparent difference in alpha-chain J-region usage or in the CDR3alpha sequence at the TRAV11-J15 junction between the haplotypes in TRAV11-bearing NK T cells. Using Biacore and tetramer-binding and decay assays, we have determined that the interaction between Tcra(c) TRAV11*01 NK T TCR and the mCD1/alpha-GalCer complex is slightly weaker than that of Tcra(b) (i.e., TRAV11*02) NK T TCR. These differences are minor compared with differences between agonist and antagonist ligands in other TCR systems, suggesting that it is unlikely that TCR polymorphism explains the defect in NK T cells in the autoimmune mouse strains. |
