Surprisingly minor influence of TRAV11 (Valpha14) polymorphism on NK T-receptor mCD1/alpha-galactosylceramide binding kinetics.

摘要: Defects in natural killer T (NK T) cell function and of interleukin-4 -production SJL NOD mice have been linked to susceptibility autoimmune disease. As both carry the T-cell receptor (TCR) alpha-chain locus "c" (Tcra(c)) haplotype, found few other strains, we attempted determine influence Tcra polymorphism on NK recognition ligand, selection, immune responses. The majority cells use an "invariant" TRAV11J15 (previously called AV14J18 or Valpha14 Jalpha281) alpha- chain paired with either TRBV13-2, BV29, BV1 recognize ligands presented by mCD1 molecules, including glycolipid alpha-galactosylceramide (alpha-GalCer). Sequencing TRAV11 from mouse strains B10.A (encoding Tcra(b) haplotype), B10.A- Tcra(c), shows that Tcra(c) has a single gene (TRAV11*01) expressed (TRAV11*02), plus closely related pseudogene. There is no apparent difference J-region usage CDR3alpha sequence at TRAV11-J15 junction between haplotypes TRAV11-bearing cells. Using Biacore tetramer-binding decay assays, determined interaction TRAV11*01 TCR mCD1/alpha-GalCer complex slightly weaker than (i.e., TRAV11*02) TCR. These differences are minor compared agonist antagonist systems, suggesting it unlikely explains defect strains.