T cell receptor haplotypes in families of patients with insulin‐dependent diabetes mellitus

SUMMARY The frequencies of Bgl 11 and Bam H1 restriction fragment length polymorphisms (RFLP) of Cβ Vβ8, Vβ11 and Vβ7.2 have been defined in a healthy Australian population. Linkage disequilibrium between alleles of the T cell receptor (TCR) Vβ8 and Vβ11 gene segments has been confirmed. We have also confirmed the lack of linkage disequilibrium between either of these loci and alleles at Cβ or Vβ7.2. Using RFLPs at Vβ11 and Vβ8 loci TCR β haplotypes have been identified in five families in which the probands have insulin‐dependent diabetes mellitus (IDDM). An extremely rare haplotype. marked by the higher molecular weight Bam H1 allele (H, H) at each of Vβ11 and Vβ8, was found in the DR4+ DR3− probands of two families (P= 0·004). In three families in which the probands had DR3. the more common TCR haplotype LH (Vβ11, Vβ8) was found. Taken together, these data confirm that linkage disequilibrium does exist in the TCR β locus, at least in some regions, and suggest that detailed analysis of the relationship between TCR Vβ haplotypes and HL A is warranted since these RFLPs may be markers for important allelic V gene sequence variations.