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T cell receptor ß chain genotyping in Australian relapsing-remitting multiple sclerosis patients

Department of Clinical Immunology, Westmead Hospital, Westmead 2145 New South Wales, Australia

Bruce H Bennetts

Department of Clinical Immunology, Westmead Hospital, Westmead 2145 New South Wales, Australia

Robert NS Heard

Department of Clinical Immunology, Westmead Hospital, Westmead 2145 New South Wales, Australia

Graeme J Stewart

Department of Clinical Immunology, Westmead Hospital, Westmead 2145 New South Wales, Australia

This study focused on susceptibility to MS within the b-chain of the T-cell antigen receptor (TCRB locus, 7q35) in a cohort of 122 RR-MS patients compared with 96 normal individuals using biallelic polymorphisms across the bv8s1(Vb8.1) to bv11s1 (Vb11) TCRB subregion. The markers bv6s5, bv8s1, bv10s1, bv15s1 and bv3s1 were studied for allele and genotype frequencies; haplotypes were assigned with combinations of two of these markers and stratification for HLA-DR15 was also performed. Linkage disequilibrium was found between alleles of the bv8s1, bv10s1/bv15s1 and bv3s1 loci in both patients and controls. An increase among RR-MS patients in the allele frequency of bv8s1*2 (P=0.03) and the haplotype bv8s1*2/bv3s1*1 (P=0.006) was noted and both were found to be statistically significant. In the DR15-positive group, the association between TCRB and MS was seen with the bv8s1*2 allele (P_uc=0.05) and the bv8s1*2/bv10s1 haplotypes (P_uc=0.048), while the haplotype associations seen among DR15-negative RR-MS patients included the bv3s1*1 allele (bv10s1*1/bv3s1*1, P_uc=0.022; bv8s1*2/bv3s1*1, P_uc=0.048). These results support the involvement of the TCRB region in MS susceptibility and encourage further study of the variable gene segments in this region.

Key Words: multiple sclerosis • TCRB region • susceptibility • haplotype • HLA

Multiple Sclerosis, Vol. 6, No. 3, 140-147 (2000)
DOI: 10.1177/135245850000600302


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